Recent advances in mining hypolipidemic bioactive compounds from animal-derived foods

Abstract

Hyperlipidemia, a prevalent chronic condition, significantly threatens human health. Growing evidence indicates that bioactive components from animal-derived foods exhibit promising hypolipidemic potential. However, their role in hyperlipidemia management has not been fully recognized. This review systematically compiles the latest findings on mining hypolipidemic bioactive compounds through the valorization of animal-derived foods. It emphasizes innovative extraction techniques and summarizes the hypolipidemic properties and molecular targets of different compounds. Their mechanisms of action are explored, encompassing both direct involvement in lipid metabolism (such as the regulation of fat, cholesterol, and bile acid metabolism) and indirect modulation (such as the impact on the gut microbiota, glucose metabolism, inflammation, and oxidative stress). Lastly, future research directions are proposed, including by-product utilization, virtual screening, system construction, multi-target and biomarker mining, and clinical research promotion. This review aims to promote the high-value utilization of animal-derived foods and contribute towards the development of more targeted hypolipidemic functional foods.

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Introduction

Hyperlipidemia, a prevalent chronic disorder characterized by lipid metabolism abnormalities, is commonly induced by unhealthy lifestyle choices or linked to other diseases. Clinically, it is manifested by abnormal levels of one or more lipid parameters, including total cholesterol (TC), total triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C).¹ The rising prevalence and mortality rates associated with hyperlipidemia, coupled with its role as a significant risk factor for cardiovascular diseases, have spurred intense research into its prevention and treatment.² With advancing research, dietary interventions have emerged as a viable strategy for managing hyperlipidemia, particularly in controlling residual cholesterol to reduce the risk of future cardiovascular events. Consequently, the exploration of food-derived bioactive compounds for the development of hypolipidemic functional products has gained increasing attention.

Animal-derived foods contain high-quality proteins, biocompatible polysaccharides, abundant essential amino acids and fatty acids, as well as micronutrients with high bioavailability, all of which play an important role in every stage of life.^3,4 However, excessive intake of animal-derived foods has been linked to an increased risk of cardiovascular diseases, leading to relatively less focus on their potential hypolipidemic effects compared to that on plant-derived foods. With the advancement of the valorization of animal-derived foods, bioactive compounds of animal-derived foods (AFBCs) are being increasingly recognized for their hypolipidemic potential. For instance, camel milk protein hydrolysates have demonstrated the ability to inhibit pancreatic lipase and cholesterol esterase in vitro—key enzymes involved in lipid metabolism—indicating potential for reduced lipid absorption and accumulation.⁵ Phospholipids derived from sea cucumbers have been shown to exert hypolipidemic effects by modulating pathways associated with cholesterol synthesis and bile acid metabolism.⁶ Specific components of animal-derived foods, such as carnosine,⁷ taurine,⁸ and astaxanthin, have also been identified for their ability to regulate dyslipidemia.⁹ Furthermore, bioactive compounds from animal-derived food by-products, including bones, blood, and internal organs, also show hypolipidemic activity. These findings underscore the importance of animal-derived food valorization in identifying hypolipidemic bioactive compounds. This not only contributes to the value development of animal-derived foods but also opens up opportunities for the creation of supplementary hypolipidemic functional products. However, further investigation is required to fully understand the hypolipidemic effects of AFBCs.

This review aims to consolidate current research on hypolipidemic bioactive compounds derived from animal-derived foods, with an emphasis on novel extraction methods, their primary hypolipidemic properties, and associated molecular mechanisms. Additionally, future research directions are explored, including the high-value utilization of by-products, virtual screening of bioactive compounds, the development of composite and delivery systems, in-depth target and biomarker discovery, and the advancement of clinical research. The objective is to provide valuable insights for the further exploration and industrial application of hypolipidemic AFBCs.

Types of AFBCs and their hypolipidemic effects

Animal-derived foods, including meat, eggs, milk, and aquatic products, contain not only common bioactive compounds but also specific active substances. These bioactive components contribute to the hypolipidemic effect to varying extents through their properties. This section summarizes the extraction methods and hypolipidemic properties of proteins and peptides, functional lipids, polysaccharides and oligosaccharides, and other AFBCs, with a particular focus on emerging extraction techniques and common hypolipidemic properties. Table 1 presents examples of the extraction methods and hypolipidemic effects of certain AFBCs.

Table 1 The hypolipidemic effects of AFBCs

Animal-derived food name	Bioactive compound name	Extraction method	Experimental model and dosage	Effects & mechanisms
a “—” represents no relevant information or no detection; “↑” denotes an increase; “↓” denotes a decrease; and “ns” indicates no significant change.
Hozami camel milk^5	Protein hydrolysates	Enzymolysis (gastric hydrolysates)	In vitro biochemical experiments	Pancreatic lipase inhibition (IC50 = 0.07 ± 0.002 mg mL^−1); cholesterol esterase inhibition (IC50 = 0.10 ± 0.002)
Chicken blood^122	Protein hydrolysates	Enzymolysis (alcalase and protamex hydrolysates)	In vitro biochemical experiments	Bile acid binding capacity (21.78% and 22.97%)
Ruditapes philippinarum ^22	Peptides	Microbial fermentation	High-fat diet in Kunming mice (600 mg kg^−1 d^−1 for 6 weeks)	Promoted lipolysis and inhibited lipogenesis, regulated gut microbiota (p-AMPK, HSL, PPARα, PPARγ ↑; Firmicutes↓, Bacteroidetes↑ Campilobacterota, Deferribactota↓ norank_f_Muribaculaceae, Muribaculum↑)
Silver carp muscle^21	Peptides	Enzymolysis (alcalase hydrolysates)	Western diet in ApoE^–/– mice (600 mg kg^−1 d^−1 for 12 weeks)	Regulated cholesterol synthesis and esterification (HNF1α, NPC1L1, ACAT2, PCSK9↓; LDLR↑)
Antarctic krill oil^35	Lipids	Supercritical fluid extraction	High-fat diet in ICR mice (400 mg kg^−1 d^−1 for 12 weeks)	Inhibited lipid synthesis, regulate glucose metabolism and hepatic antioxidant activities (C/EBP-α, C/EBP-β, SREBP1, PPARγ, FAS, ACC1, leptin↓ PPARα, UCP2, AMPK-α1, AMPK-α2, adiponectin↑)
Xestospongia muta^36	Linoleic acid	Organic solvent extraction	HepG2 cells (50 μg mL^−1)	Increased HDL cholesterol uptake (SR-BI ↑)
Cow's milk^41	Polar lipids	—	High-fat diet in Ldlr^−/− mice (2% added by weight for 14 weeks)	Reduced lipoprotein cholesterol, lowered inflammation and regulated gut microbiota (SCD1, CCL4, CCL2, ADGRE11↓ HMGCR↑; Firmicutes/Bacteroidetes↓ Actinobacteria↑)
Sea cucumber^6	Phospholipids	Organic solvent extraction	High-fat diet in ApoE^−/− mice (0.03% of the diet content for 12 weeks)	Regulated cholesterol synthesis and bile acid metabolism (SQLE ↓ HMGCR,ABCA1,CYP7A, CYP27A1, LAMP1, ABCB11↑)
Sturgeon skull^50	Chondroitin Sulfate	Enzymolysis	High-fat diet in C57BL/6J mice (400 mg kg^−1 d^−1 for 12 weeks)	Regulate liver metabolism and gut microbiota (arachidonic acid, docosahexaenoic acid, and androsterone↓ cholic acid↑ Firmicutes↑)
Bovine milk^51	Glycosaminoglycans	Enzymolysis	3T3-L1 cells (50 μg ml^−1)	Inhibited fat synthesis (PPAR-γ, C/EBP-α, SREBP1c, FAS↓)
Pearsonothuria graeffei^52	Fucosylated chondroitin sulfate	Enzymolysis	High-fat diet in C57BL/6J mice (80 mg kg^−1 d^−1 for 10 weeks)	Inhibited lipid synthesis, increased lipolysis and thermogenesis, regulate gut microbiota (CD36, L-FABP, DGAT1, DGAT2, MTP, GPD1↓ PPARγ, UCP1, PGC-1α, ATGL, UCP1↑; Firmicutes/Bacteroidetes↓ Desulfobacterota↓)
Patinopecten yessoensis skirte^55	Acidic polysaccharides	Enzymolysis	High-fat diet in BALB/c mice (300 mg kg^−1 d^−1 for 8 weeks)	Regulated lipid metabolism, amino acid metabolism and gut microbiota (total SCFAs, acetic acid, butyric acid↑; Lachnoclostridium↑)
No detailed description of the source^68	Chitobiose	Enzymolysis	High-fat diet in ob/ob^−/− mice (500 mg kg^−1 d^−1 for 10 weeks)	Promoted lipid β-oxidation and regulated SCFAs synthesis (FXR, ACSL1, PPARα, CPT1A, CPT2, ACOX1↑ propionic acid, butyric acid, total SCFAs↑)
Crab^65	Chitooligosaccharides	—	T2DM Kunming mice with high-fat diet (140 mg kg^−1 d^−1 for 5 weeks)	Regulate cholesterol synthesis and degradation, blood glucose metabolism and gut microbiota (HMGCR, SMYD3↓ CYP7A1, GLP-1↑; Proteobacteria↓ Firmicutes/Bacteroidetes, Verrucomicrobiales↑)
No detailed description of the source^72	Taurine	—	High-fat diet in C57BL/6J mice (250 mg kg^−1 d^−1 for 12 weeks)	Inhibited fat synthesis, promoted lipid β-oxidation and mitigated inflammation (SIRT1, NAD^+/NADH, PPARγ, SREBP1c, FAS, NF-κB↓ AMPK, FOXO1, PGC1α, PPARα, LXRβ↑)
No detailed description of the source^9	Astaxanthin	—	RAW264.7 cells (50 μM)	Promoted cholesterol efflux (ABCA1, ABCG1, SR-BI↑ circTPP2↑ miR-3073b-5p↑)
Marine horseshoe crab^73	Kynurenic acid	Organic solvent extraction	High-fat diet in Kunming mice (5 mg kg^−1 d^−1 for 8 weeks)	Regulated gut microbiota (Firmicutes/Bacteroidetes↓ Lachnospiraceae_UCG-006, Lactococcus, Roseburia↓ Alistipes↑)

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Proteins and peptides

Animal-derived foods are rich in proteins, which play an important role in maintaining the basic physiological activities of the organism. Common animal-derived proteins include collagen, keratin, and whey protein. Traditional extraction methods include salting-out extraction, alkali- or acid-based approaches, and enzymatic extraction. With research progress, more environmentally friendly and efficient techniques are emerging for protein extraction. For example, a deep eutectic solvent composed of urea and acetic acid has been used for silver carp collagen extraction, showing enhanced solubility and gel properties while improving the recovery rate compared to those of traditional acid extraction methods.¹⁰ Similarly, ionic liquid-based magnetic adsorbents have been applied to whey protein extraction, offering simultaneous and efficient isolation of multiple functional proteins while utilizing adsorbents with high selectivity and renewability, alongside a simple and rapid process.¹¹ The composite application of multiple technologies is becoming increasingly popular in extraction methods, with ultrasound-assisted extraction being the most commonly used approach. The combined use of multiple technologies, particularly ultrasound-assisted extraction, is becoming increasingly prevalent. Ultrasonic treatment during acid extraction improves the solubility, antibacterial properties, and heparin-binding ability of Coregonus peled protamine.¹² Ultrasound-assisted deep eutectic solvent extraction has demonstrated a 30% increase in the protein yield from tilapia viscera compared to single-method extraction.¹³ These innovations in extraction methods expand the potential for valorizing animal-derived protein resources.

Additionally, animal proteins offer advantages over plant proteins in terms of amino acid composition, in vivo digestibility, and processing properties.¹⁴ These properties also influence the hypolipidemic effect of animal protein to a certain extent. Research indicates that avian proteins can regulate HDL characteristics in ApoE^−/− mice in a sex-specific manner.¹⁵ Pork protein has been shown to reduce serum TG levels in obese mice, an effect attributed to its high branched-chain amino acid content.¹⁶ When incorporated into high-fat food matrices, pork and chicken proteins, with their salt-soluble properties, are more effective than casein and soy protein in binding bile acids, thus reducing the efficiency of fat digestion during intestinal digestion.¹⁷ Moreover, the hypolipidemic effects of animal proteins vary depending on their sources. Chicken, pork, beef, and fish proteins have been shown to regulate liver lipid and energy metabolism-related genes in rats to varying degrees.¹⁸

The hypolipidemic effects of proteins are closely tied to the release of bioactive peptides during hydrolysis. For instance, camel milk protein hydrolysate, generated through simulated gastrointestinal digestion, exhibits stronger pancreatic lipase inhibitory activity compared to undigested proteins.⁵ Similarly, digested egg white hydrolysates show enhanced bile salt-binding ability, attributed to smaller particle sizes, reduced sulfhydryl content, and increased hydrophobic group exposure during digestion.¹⁹ Inhibition of digestive enzymes and bile acid binding, both of which affect cholesterol absorption and excretion, are crucial mechanisms through which bioactive peptides exert their hypolipidemic effects. These effects are also influenced by the molecular weight of the peptide components. Low molecular weight peptides tend to have higher bioavailability, potentially enhancing hypolipidemic effects, while high molecular weight peptides are more likely to form peptide–microparticle complexes that facilitate binding. Amino acid composition is also an important factor affecting hypolipidemic activity. In a study, it was proposed that peptides containing arginine and aromatic amino acids are more conducive to binding pancreatic lipase and cholesterol esterase than glutamic acid and aspartic acid, and the specific position of the amino acid in the peptide will also affect the binding force.²⁰ Enzyme extraction and microbial fermentation are the most commonly employed methods for obtaining bioactive peptides. Additionally, biosynthetic peptides, which mimic natural bioactive peptide sequences, are increasingly being explored in research. For example, silver carp muscle peptides obtained through alkaline protease hydrolysis have been shown to reduce cholesterol levels by inhibiting genes related to intestinal cholesterol absorption and upregulating low-density lipoprotein receptor (LDLR) expression in Caco-2 cells and animal models.²¹ Similarly, bioactive peptides from Ruditapes philippinarum, fermented by Bacillus natto, alleviate hyperlipidemia in mice by modulating lipolysis-related genes and downregulating lipid synthesis-related genes.²² Whey protein-derived synthetic peptides help maintain cholesterol homeostasis by promoting intestinal cholesterol efflux and upregulating LDLR expression.²³

As discussed, the hypolipidemic effects of animal proteins and peptides primarily include the inhibition of digestive enzymes, bile acid binding, and activation of lipid metabolism-related targets. Due to their amino acid composition and hydrophobic interactions, these peptides positively influence lipid absorption and excretion. The use of peptides derived from proteins can be viewed as a strategy to enhance the hypolipidemic effects of proteins; however, their efficacy is still contingent on the inherent properties of the parent protein.

Functional lipids

Functional lipids, a major class of bioactive compounds in animal-derived foods, play roles beyond energy supply and cell membrane integrity maintenance. Their most significant function lies in exerting specific biological activities. These lipids can be categorized into glycerides, fatty acids, and lipoids, with common functional lipids including fish oil, krill oil, and polar lipids.²⁴ The extraction methods for these lipids range from traditional organic reagent extraction to emerging techniques such as supercritical CO₂ extraction, accelerated solvent extraction, green solvent extraction, and various composite-assisted extraction methods.²⁵ A key focus in lipid extraction is obtaining high-quality, stable components in an environmentally sustainable and efficient manner, with recent advancements offering effective solutions. For example, low-temperature continuous phase extraction technology has been shown to yield Antarctic krill oil with higher yield and better oxidation stability.²⁶ Applying micro-aqueous cold extraction to salmon head oil achieved a 93% recovery rate while reducing oxidation and undesirable flavor.²⁷ The combination of green ultrasound-assisted technology, adsorbent purification, and antioxidant-assisted refining in rainbow trout intestinal oil extraction successfully increased the content of essential polyunsaturated fatty acids (PUFAs).²⁸ Additionally, structural lipid modification has gained attention as a promising area of research. Medium- and long-chain triacylglycerols (MLCT), rich in n-3 PUFAs with higher bioavailability, can be prepared through bio-imprinted lipase-catalyzed interesterification using fish oil and medium-chain TG as raw materials.²⁹ High-purity 1,3-diacylglycerol (DGA) obtained from duck oil using an alkali hydrolysis-lipase esterification method achieved a yield exceeding 94%. Furthermore, microencapsulation was beneficial in inhibiting the oxidation process of 1,3-DGA and enhancing its stability.³⁰

The hypolipidemic properties of functional lipids are particularly advantageous as they directly participate in lipid resynthesis and metabolism as exogenous lipids, while also regulating lipid distribution by integrating into cell membranes. The properties of the lipid structure provide the potential to compete with cholesterol for absorption sites. Fatty acids, including saturated and unsaturated fatty acids, are key components of functional lipids. Animal lipids often contain a higher proportion of saturated fatty acids, which are often considered to be harmful to the health of the body. There is one of the reasons that limit the exploration of animal lipids in hypolipidemic activity. Recent studies have shown that odd-chain saturated fatty acids that mainly exist in animal-derived foods show great hypolipidemic potential. For instance, pentadecanoic acid, the odd-chain saturated fatty acid, that is often present in milk, can effectively reduce LDL levels in female patients with nonalcoholic fatty liver disease and help to form a beneficial gut microbiota structure.³¹ In addition, low-concentration intake of the pentadecanoic acid was beneficial in alleviating oxidative stress and reducing blood lipid levels of the offspring.³² Another odd-chain fatty acid, heptadecanoic acid, although not explicitly shown to have excellent hypolipidemic activity, has also been shown in epidemiology to be associated with low lipid levels.³³ The level of odd-chain fatty acids in the body is not only directly related to the supplementation of bioactive compounds, but also related to the regulation of the gut micrbiota and lipid distribution by them. Research on unsaturated fatty acids, particularly PUFAs, has intensified, with n-3 PUFAs—found primarily in fish oil—being the main focus of hypolipidemic products. Different forms of n-3 PUFAs exert distinct regulatory roles in lipid metabolism. Compared to DHA/EPA-phospholipid (PL) and EPA/DHA-triacylglycerol (TAG), krill oil has been proven to be more effective in lowering LDL-C levels in mice. This may be attributed to the fact that n-3 PUFAs in the phospholipid form are more readily absorbed and incorporated into cell membranes.³⁴ Krill oil has also been shown to down-regulate lipogenesis genes while up-regulating genes involved in lipolysis and β-oxidation.³⁵ Thus, the form of n-3 PUFAs, in addition to their content and purity, has become an important consideration in the lipid extraction process. While n-6 PUFAs are less frequently studied, they also contribute to hypolipidemic effects. For example, linoleic acid-rich components from Xestospongia muta significantly increased the expression of the scavenger receptor class B type 1 (SR-BI) by 129% in HepG2 cells.³⁶ Additionally, conjugated linoleic acid, a mixture of linoleic acid isomers predominantly found in dairy products and ruminant meat, was shown to markedly reduce serum TG, TC, leptin, adiponectin, and non-esterified fatty acid levels in mice fed a high-fat diet.³⁷ As research progresses, an appropriate n-6/n-3 PUFA ratio is increasingly recognized as a key factor influencing hypolipidemic effects,³⁸ but the specific relationship requires further clarification.

Phospholipids, another vital class of functional lipids abundant in dairy products and eggs, exert hypolipidemic effects through their regulation of lipid distribution and intestinal absorption. Egg-derived phospholipids reduce cholesterol absorption by maintaining phospholipid saturation in the small intestine and also influence cholesterol synthesis, intake, and excretion. Furthermore, they can lower serum TG levels by modulating glyceride distribution.³⁹ Similarly, a study has indicated that egg-derived phosphatidylcholine was more effective than soy-derived phosphatidylcholine in regulating lipid levels, which may be associated with its regulation of glycerophospholipid metabolism. These pieces of evidence suggested a close link between lipid redistribution and hypolipidemic effects.⁴⁰ Supplementation with 2% milk sphingomyelin resulted in a 51% reduction in serum TC levels in Ldlr^−/− mice, suggesting its role in regulating the gut microbiota and reducing inflammation.⁴¹ Phospholipids from sea cucumber have been shown to regulate cholesterol synthesis and bile acid metabolism in ApoE^−/− mice.⁶ Beyond PUFAs and phospholipids, structural lipids such as 1,3-dioleoyl-2-palmitoylglycerol (OPO)⁴² and shark liver oil rich in alkyl glycerol⁴³ exhibit hypolipidemic effects, primarily through their antioxidant and anti-inflammatory properties.

These examples demonstrate that animal-derived functional lipids exert their hypolipidemic effects primarily by participating in lipid metabolism, regulating lipid distribution, and exerting anti-inflammatory and antioxidant properties. Fish oil, abundant in n-3 PUFAs, is most commonly utilized to reduce TG levels. Animal-derived phospholipids have been shown to play an active role in cholesterol metabolism, indicating their potential as specific adjuncts in the development of hypocholesterolemic products.

Polysaccharides and oligosaccharides

Animal-derived polysaccharides are widely used in biomaterials and healthy nutrition due to their specific physicochemical properties and biological activities.⁴⁴ Glycosaminoglycans are the most prevalent linear acidic polysaccharides found in animal-derived raw materials, including chondroitin sulfate, dermatan sulfate, heparin, and hyaluronic acid. Common extraction methods for animal polysaccharides include water extraction, acid- and alkali-based methods, enzyme-assisted extraction, and combined extraction techniques.⁴⁵ Given the relatively low proportion of polysaccharides in animal-derived foods, which are typically rich in proteins and fats, effectively removing impurities to enhance yield and purity is a primary concern in the extraction process. Recent studies have introduced new methods for extracting proteins and lipids, contributing to more efficient polysaccharide extraction. For instance, chondroitin sulfate can be obtained with a 62.72% extraction rate and 85.96% purity by combining enzyme treatment, ultrasound, and hollow fiber dialysis.⁴⁶ The ionic liquid-assisted enzyme extraction method has increased the extraction rate of dermatan sulfate from 57% to 75%, eliminating the need for harsh chemicals and reducing extraction time.⁴⁷ Moreover, certain methods also maintain or enhance the biological activity of polysaccharides. For example, fermentation-assisted extraction using Enterococcus hirae GS22 has been shown to improve the functional activity of sea cucumber intestinal polysaccharides.⁴⁸

The physical properties of polysaccharides, such as their micelle formation, adsorption, or ion exchange capacity,⁴⁹ along with their functional activities like immune modulation, antioxidation, and hypoglycemic effects, can significantly influence blood lipid regulation.^44,45 Among them, chondroitin sulfate is one of the most studied glycosaminoglycan in the study of hypolipidemic activity. Chondroitin sulfate derived from sturgeon heads has been shown to significantly reduce serum TC, LDL-C, and TNF-α levels in obese mice, while also alleviating the accumulation of TG and TC in the liver. This regulation involves multiple metabolic pathways, including primary bile acid biosynthesis.⁵⁰ Bovine milk glycosaminoglycans, primarily composed of chondroitin sulfate, have been demonstrated to down-regulate genes associated with adipogenesis and differentiation in 3T3-L1 cells.⁵¹ Fucosylated chondroitin sulfate supplementation significantly reduced serum TC, LDL-C, and ApoB-48 levels in obese mice, while also regulating proteins involved in intestinal lipid synthesis and degradation.⁵² The hypolipidemic properties of sea cucumber sulfated polysaccharides are related to fucose branching and sulfation patterns.⁵³ Higher branching and molecular weight in the regulation of metabolic homeostasis may be linked to better biological activity.⁵⁴ Furthermore, acidic polysaccharides from skirts with heparin-like and chondroitin sulfate-like core backbones,⁵⁵ glycosaminoglycans extracted from fish waste,⁵⁶ and dermatan sulfate derived from pig mucosa⁵⁷ have been found to exert hypolipidemic effects by regulating amino acid metabolism, inhibiting lipase activity, modulating bile acid binding capacity, and reducing pro-inflammatory lipids in brown fat, respectively. These findings highlight the significant potential of glycosaminoglycans with hypolipidemic effects. As components of the extracellular matrix, they offer high biocompatibility and possess diverse functional activities, playing a pivotal role in their hypolipidemic effects. On the other hand, glycosaminoglycans also act as receptors. Liver heparan sulfate proteoglycans have been shown that are PCSK9 receptors and essential for lipid regulation.⁵⁸ In a study on the mechanism of cancer cells against ferroptosis, it was mentioned that glycosaminoglycans on the surface of cancer cells promoted lipoprotein uptake more significantly than traditional lipoprotein receptors LDLR.⁵⁹ Although this study showed that glycosaminoglycan was a key mediator for tumor cells to escape ferroptosis, it also undoubtedly gave a hint that exogenously supplemented glycosaminoglycans may have the potential to remove excess lipoproteins in the blood. However, research on glycosaminoglycans other than chondroitin sulfate remains limited, and further investigation is needed to explore the specific mechanisms of action and potential differences between various types of glycosaminoglycans in lipid regulation.

In addition to glycosaminoglycans, chitosan and chitooligosaccharides, primarily derived from crustaceans, also exhibit significant hypolipidemic activity. A meta-analysis has indicated that chitosan provides a cholesterol-lowering effect comparable to that of pharmaceutical interventions, without negatively impacting the intestinal mucosa.⁶⁰ Oligosaccharides, which have a lower molecular weight than polysaccharides, are often products of polysaccharide degradation. Recent studies have employed methods such as microbe-specific enzyme degradation and photocatalytic degradation to obtain them.^61,62 Due to variations in intestinal absorption, polysaccharides and oligosaccharides display different hypolipidemic effects. A comparison of chitosan and chitooligosaccharides in rats revealed that chitosan more effectively reduces lipid peroxidation, promotes lipid excretion, and alleviates hepatic lipid accumulation, attributed to its superior lipid adsorption properties. In contrast, chitooligosaccharides, with lower lipid adsorption capacity, reduce lipid absorption by decreasing the expression of fatty acid-binding proteins 2 and 4 (FAP2 and FAP4).⁶³ Chitooligosaccharides can also regulate blood lipids by activating the AMPK-SPT1-SCD1 pathway to inhibit lipid production,⁶⁴ inhibiting histone methyltransferase SET and MYND domain-containing protein 3 (AMYD3) to regulate the key enzyme 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) for cholesterol synthesis,⁶⁵ and improving bile acid synthesis.⁶⁶ Furthermore, certain oligosaccharides exert hypolipidemic effects by influencing intestinal function. For example, sialic acid and 3-sialic lactose, derived from the milk matrix, regulate genes associated with intestinal mucus synthesis, digestion, and absorption, thereby exerting hypolipidemic effects.⁶⁷ Chitobiose can mediate lipid metabolism by promoting butyric acid production.⁶⁸

From the above examples, it is evident that the hypolipidemic effects of animal-derived polysaccharides and oligosaccharides can be regulated in multiple ways through their physical and functional properties. Because animal-derived polysaccharides often have more complex structures, the structure–activity relationship or the interaction with the gut microbiota embodied in their hypolipidemic effects needs to be further understood.

Others

In addition to well-known bioactive compounds, animal-derived foods contain trace components with hypolipidemic effects, such as astaxanthin, taurine, and L-carnitine. Despite the availability of various environmentally friendly and efficient extraction methods, limited concentrations of these compounds often necessitate biosynthesis for their acquisition. Additionally, these substances are sometimes co-extracted during the isolation of other bioactive compounds. For instance, the extraction of functional lipids frequently results in the concurrent isolation of astaxanthin. A recent study employing subcritical and supercritical fluid extraction successfully obtained PUFA-rich edible oils and taurine-enriched hydrolysates from yellow corvina by-products.⁶⁹ Similarly, a four-liquid-phase system was applied to extract crude oil from Antarctic krill, effectively separating four primary components—phospholipids, proteins, saccharides, and astaxanthin—via hydrophobic and hydrophilic phase partitioning.⁷⁰ These findings indicate that the efficient separation of multiple bioactive compounds could be a promising avenue for extracting specific active ingredients from animal sources in the future. Regarding hypolipidemic activity, taurine, a prominent component of seafood, regulates bile acid metabolism and enhances neutral sterol excretion by upregulating Ruminiclostridium levels.⁷¹ Recent studies have also highlighted taurine's role in activating the SIRT1/AMPK/FOXO1 signaling pathway to regulate lipid metabolism⁷² and mitigate abnormal amino acid metabolism.⁸ Astaxanthin promotes cholesterol efflux in foam cells by modulating the ircTPP2/miR-3073b-5p/ABCA1 pathway.⁹ Kynurenic acid, derived from marine horseshoe crabs, demonstrates potent hypolipidemic effects by reversing the increased Firmicutes to Bacteroidetes ratio in hyperlipidemic mice, likely due to its antioxidant properties.⁷³ In addition, other bioactive compounds with lipid-lowering effects, such as selenocysteine,⁷⁴ lipoic acid,⁷⁵ and heme,⁷⁶ can also be found in animal-derived foods. These substances may be more in the form of biosynthetic compounds applied in various studies. However, this also undoubtedly reveals the great potential of animal-derived foods in exploring hypolipidemic substances. These bioactive compounds in animal-derived foods also contribute to hypolipidemic effects through various mechanisms. The continued exploration of unique AFBCs with hypolipidemic properties will facilitate the high-value utilization of animal-derived foods.

The overview of extraction methods and hypolipidemic effects of various AFBCs underscores the significant potential for the valorization of animal-derived foods in this field (Fig. 1). Extraction techniques are progressively moving towards more sustainable and efficient approaches, with a focus on composite extraction methods to optimize both efficiency and purity. The integration of in vivo and in vitro experimental analyses for functional activity evaluation is crucial for elucidating the hypolipidemic role of AFBCs.

Fig. 1 The extraction methods and hypolipidemic properties of the main bioactive components from animal-derived foods.

The hypolipidemic mechanisms of animal-derived foods

Hyperlipidemia is a multifactorial disorder characterized by dysregulated lipid homeostasis, involving various regulatory pathways. It is commonly associated with conditions such as obesity, hyperglycemia, and nonalcoholic fatty liver disease. Consequently, both direct and indirect regulatory mechanisms contribute to lipid metabolism. This section outlines the direct and indirect hypolipidemic mechanisms of AFBCs.

Direct regulation mechanism

Regulation of fat absorption, synthesis and decomposition. Excessive fat accumulation is a primary contributor to hyperlipidemia. AFBCs can modulate lipid levels by regulating fat absorption, fat synthesis, and lipolysis (Fig. 2). In terms of fat absorption, certain animal-derived proteins and peptides have been shown to inhibit pancreatic lipase and cholesterol esterase, thus reducing the formation of free lipids and fat absorption. Inhibition of endogenous fat synthesis plays an even more critical role in lipid metabolism. Fat synthesis involves TG and fatty acid production, and compounds such as fucosylated chondroitin sulfate, chitobiose, and egg protein peptides can affect TG synthesis by inhibiting key enzymes such as glycerol-3-phosphate dehydrogenase 1 and diacylglycerol acyltransferases 1 and 2 (GPD1, DGAT1, and DGAT2). Additionally, the inhibition of cluster of differentiation 36 (CD36) and liver fatty acid binding protein (L-FABP), which are involved in fatty acid uptake, further contributes to the reduction of fat synthesis.^52,68,77 Key enzymes in fatty acid synthesis include ATP-citrate lyase (ACL), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS). Bempedoic acid, a hypolipidemic drug, reduces lipid synthesis by inhibiting ACL activity in vivo.⁷⁸ Meretrix lusoria enzymatic hydrolysate can inhibit key enzymes involved in fatty acid synthesis, including FAS, ACC, stearoyl-CoA desaturase (SCD), pyruvate dehydrogenase kinase (PDK), and carnitine palmitoyltransferase (CPT), in db/db mice by activating AMP-activated protein kinase (AMPK), thus regulating lipogenesis.⁷⁹ Sterol regulatory element-binding protein 1 (SREBP-1), an essential transcription factor for adipogenesis, regulates genes like acetyl-CoA carboxylase α (Acaca), FAS, and SCD1, while also influencing adipogenesis through peroxisome proliferator-activated receptor gamma (PPARγ) expression. Both milk glycosaminoglycan and krill oil inhibit adipogenesis by downregulating CCAAT/enhancer-binding protein alpha (C/EBP-α), SREBP-1, PPARγ, and FAS. Milk glycosaminoglycan has been shown to reduce PPARγ and C/EBP-α expression by 40% and 20%, respectively.^35,51 In promoting lipolysis, various enzymes involved in TG hydrolysis and fatty acid β-oxidation, such as adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), CPT1, and CPT2, play critical roles.⁵² Among these, PPARα is the most pivotal regulatory protein in lipolysis. Fibrates, as PPAR activators, modulate lipolysis by inhibiting HSL while upregulating PPARα to enhance fatty acid breakdown. Bioactive peptides from Ruditapes philippinarum regulate lipolysis by upregulating HSL, p-AMPK, and PPARα.²² Chitobiose modulates PPARα expression by activating the farnesoid X receptor (FXR), which in turn regulates the expression of downstream genes, including CPT1A and CPT2. Additionally, accumulated butyric acid can bind to PPARα, further accelerating fatty acid degradation.⁶⁸

Fig. 2 The direct hypolipidemic mechanisms of AFBCs (the green label represents up-regulation, and the red label represents down-regulation).

Regulation of cholesterol uptake, synthesis, esterification and efflux. Elevated circulating cholesterol levels are a major risk factor for cardiovascular disease, with excessive LDL deposition heightening the risk of atherosclerosis. LDL remains a primary therapeutic target in hyperlipidemia management.² Therefore, regulating cholesterol metabolism and maintaining its homeostasis are crucial for the treatment of hyperlipidemia. AFBCs can play a hypolipidemic role by regulating cholesterol uptake, synthesis, esterification, and efflux (Fig. 2). Cholesterol uptake encompasses the absorption of free cholesterol, LDL, oxidized LDL (ox-LDL), and HDL, all of which are associated with various receptors. The Niemann–Pick C1-like 1 (NPC1L1), a receptor, facilitates free cholesterol uptake and the hypolipidemic drug ezetimibe functions by inhibiting its expression. LDLR, the primary receptor for LDL, plays a key role in reducing circulating LDL. Statins enhance LDLR expression, while proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors prevent LDLR degradation. Peptides from silver carp muscle, Xuanwei ham and whey protein can reduce cholesterol absorption and cholesterol ester formation by inhibiting NPC1L1 and acetyl-CoA acetyltransferase 2 (ACAT2) through hepatocyte nuclear factor 1 alpha /4 alpha (HNF1α/HNF4α) pathways. Additionally, the former two AFBCs can enhance LDLR expression by inhibiting PCSK9 via HNF1α, further decreasing cholesterol levels.^21,23,80 HDL and ox-LDL are often recognized by scavenger receptors such as scavenger receptor class A type 1 (SR-A1), SR-BI, and CD36 through non-LDLR pathways. For instance, blue mussel hydrolysates inhibit cholesterol influx and foam cell formation by downregulating SR-A1 and CD36,⁸¹ while linoleic acid-rich components from Xestospongia muta significantly enhance SR-BI expression, promoting HDL uptake.³⁶

Regarding cholesterol synthesis, sea cucumber phospholipids have been shown to influence cholesterol production by modulating key enzymes such as HMGCR and squalene epoxidase (SQLE).⁶ Hydrolysates from chicken crude chalaza affect cholesterol synthesis by regulating squalene synthase.⁸² Chitin from Indonesian mangrove crab shells reduces HMGCR enzyme activity by 68.733% in vitro and demonstrates strong affinity in computer simulations.⁸³ HMGCR is the primary target of statins, a first-line drug for hyperlipidemia. Chitosan oligosaccharide and ruminant trans fatty acid influence HMGCR through upstream regulators like SMYD3 and SREBP2, respectively.^64,84 Additionally, chitooligosaccharides from snow crabs impact cholesterol synthesis through the AMPK-SREBP1-SCD1 pathway.⁶⁵ Since cholesterol in plasma lipoproteins predominantly exists as cholesterol esters, regulating cholesterol esterification plays a critical role in lipoprotein formation and HDL-mediated reverse cholesterol transport. AFBCs modulate cholesterol esterification by inhibiting NPC1L1 and HNF1α to regulate the key esterifying enzyme ACAT2, reducing cholesterol formation. In addition to regulating ACAT2, carp muscle hydrolysates can increase lecithin-cholesterol acyltransferase (LCAT) expression, thereby boosting serum HDL-C levels. These hydrolysates also promote the expression of ATP-binding cassette subfamily G members 5 and 8 (ABCG5 and ABCG8), enhancing cholesterol efflux.⁸⁵ Beyond regulating scavenger receptor-mediated cholesterol influx, blue mussel hydrolysates upregulate ABCA1 and ABCG1 expression, facilitating cholesterol efflux.⁸¹ Astaxanthin promotes cholesterol efflux by downregulating miR-3073b-5p and upregulating circTPP2, which in turn influences ABCA1 and enhances cholesterol excretion in RAW264.7 cells.⁹

Regulation of bile acid synthesis, transport and metabolism. Cholesterol can be converted into bile acids, a key mechanism for promoting its excretion. AFBCs exert hypolipidemic effects by regulating receptors involved in bile acid synthesis, transport, and metabolism (Fig. 2). Various enzymes play pivotal roles in bile acid synthesis, including cytochrome P450 family 7 subfamily A member 1, family 8 subfamily B member 1, and family 27 subfamily A member 1 (CYP7A1, CYP8B1, and CYP27A1) in the classical pathway, and CYP27A1 and cytochrome P450 family 7 subfamily B member 1 (CYP7B1) in the alternative pathway. Bile acid chelating agents accelerate cholesterol conversion by promoting CYP7A1 expression. Hydrolysates from crude chalaza,⁸² chitooligosaccharides,⁶⁵ and taurine⁸ also upregulate bile acid synthesis through CYP7A1 while influencing additional pathways. Taurine promotes CYP7A1 expression by inhibiting the FGF21/ERK pathway.⁸⁶ Bioactive peptides in casein hydrolysates modulate liver X receptor alpha (LXRα), influencing ABCG5 and fibroblast growth factor 19 (FGF19) expression, which inhibits CYP7A1 and CYP8B1, thereby enhancing cholesterol excretion.⁸⁷ Bile acid transport and metabolism are closely linked to synthesis-related enzymes. Carp muscle hydrolysates regulate bile acid metabolism by upregulating the bile salt export pump ABCB11 and modulating the expression of CYP7A1, CYP27A1, and CYP2C70.⁸⁵ Taurine directly enhances the expression of organic anion transport polypeptide 2 (OATP2) and betaine homocysteine methyltransferase (BHMT) in the livers of hyperlipidemic rats, influencing CYP7A1 and CYP8B1 expression.⁸⁸ Sea cucumber polysaccharides accelerate cholesterol consumption and bile acid excretion in diabetic rats by inhibiting FXR-SHP signaling, modulating CYP7A1 and bile acid-CoA synthase (BACS), and regulating the excretion and reabsorption receptors bile salt export pump (BSEP) and sodium/taurocholate cotransporting polypeptide (NTCP).⁸⁹

Indirect regulation mechanism

Regulation of the gut microbiota. Dyslipidemia disrupts gut microbiota homeostasis, and this dysbiosis can also exacerbate the process of dyslipidemia. The health index of the gut microbiota is positively correlated with HDL, highlighting the importance of gut microbiota regulation in the hypolipidemic effect.⁹⁰ Different AFBCs influence the gut microbiota in various ways, often indirectly, by altering its composition and metabolism (Fig. 3). AFBCs reduce dyslipidemia by reversing an imbalanced microbiota structure, often through a reduction in the Firmicutes/Bacteroidetes (F/B) ratio, a marker of gut dysbiosis. In dyslipidemic mice, bioactive peptides from Ruditapes philippinarum decreased Firmicutes by 25.47% and increased Bacteroidetes by 36.15%, similar to the effects of simvastatin. These peptides also downregulated the abundance of Campylobacterota and Deferribacterota, which are associated with inflammation and hyperlipidemia.²² Beyond modifying the F/B ratio, whey protein peptide VAPFPE upregulated Ruminococcaceae_UCG-014 and Ruminococcaceae_UCG-013, which were negatively correlated with liver TGs at the genus level, and promoted Bifidobacterium, which was negatively correlated with SREBP-2. Changes in these bacteria's abundance influenced lipid metabolism, contributing to the regulation of hyperlipidemia.²³ Tuna yolk glycoprotein has been shown to exert its hypolipidemic effect by increasing the beneficial bacteria Akkermansia and Lactobacillus, reducing the harmful bacteria Desulfovibrio which is positively correlated with the levels of lipids and inflammatory factors.⁹¹ Due to the diverse properties of AFBCs, different microbial communities are often enriched during the regulation process, with cross-feeding and nutritional competition contributing to the diversity of gut microbiota composition.

Fig. 3 The indirect hypolipidemic mechanisms of AFBCs (the green label represents up-regulation, and the red label represents down-regulation).

The regulation of gut microbiota metabolism is influenced both by the biological transformation of AFBCs into metabolites and by changes in the microbial community structure. Short-chain fatty acids (SCFAs) are key metabolites with hypolipidemic effects, impacting SREBP-2, ABC transporters, and CYP7A1. Supplementation with egg protein peptide IRW increases propionic acid levels, which are positively correlated with the upregulation of Parabacteroides abundance.⁷⁷ Fucoidin sulfate enriched the abundance of Rikenellaceae and Muribaculaceae which produced SCFA after treatment.⁵² Bile acids, another important metabolite, are involved in cholesterol metabolism through bacteria carrying bile acid hydrolase and 7α-dehydroxylase. In hamsters, marine chitooligosaccharides not only upregulate SCFA-producing flora but also modulate the abundance of norank_f_Muribaculaceae, Bacteroides, and Parabacteroides, which are positively associated with bile acid modification.⁶⁶ Taurine regulates bile acid metabolism and promotes cholesterol excretion by enhancing the level of Ruminiclostridium. Additionally, taurine helps improve amino acid metabolism disorders linked to hyperlipidemia.⁸ Skirt acidic polysaccharides have also been shown to influence amino acid metabolism including arginine and proline metabolism to exert their regulatory effects.⁵⁵ Recent studies have proposed amino acids as a primary carbon source for liver fat synthesis.⁹² Li et al. identified intestinal commensal bacteria that rapidly consume amino acids and their associated metabolic genes, providing insight into the mechanisms of amino acid metabolism by the gut microbiota.⁹³ This emerging research highlights the interconnection between amino acid metabolism, gut microbiota, and lipid regulation. Moreover, some secondary metabolites derived from AFBCs under the action of the gut microbiota also contribute to hypolipidemic effects. For instance, unsaturated fatty acids can convert linoleic acid into conjugated linoleic acid isomers through the action of bacteria harboring CLA-HY enzymes, thereby promoting lipid breakdown.⁹⁴ In the process of AFBCs regulating the metabolism of the gut microbiota, various metabolites interact with each other, making it essential to monitor favorable changes while minimizing potential adverse effects.

Regulation of blood glucose metabolism. Blood glucose and lipid metabolism are closely intertwined, with the energy required for lipid synthesis, breakdown, transport, and metabolism being linked to the tricarboxylic acid cycle, whose intermediates also participate in glucose metabolism. Consequently, regulation of glucose metabolism often influences lipid metabolism. AFBCs exhibit hypolipidemic effects by affecting key enzymes in gluconeogenesis, glucose transporters, or insulin signaling (Fig. 3). Collagen peptides derived from Harpadon nehereus bones significantly enhance the phosphorylation of glucokinase and glycogen synthase kinase 3 while reducing glucose-6-phosphatase and phosphoenolpyruvate carboxykinase 1 levels, thereby exerting hypolipidemic effects while regulating hyperglycemia. Additionally, the insulin-dependent glucose transporter type 4 (GLUT4) plays a pivotal role in lipid metabolism.^56,57 Chitooligosaccharides and whey protein hydrolysates elevate glucagon-like peptide-1 levels, which suppress appetite and reduce exogenous lipid intake.^65,95 Regarding insulin regulation, mussel polysaccharides modulate glucose and lipid metabolism by activating the PI3K/Akt signaling pathway and alleviating liver insulin resistance.⁹⁶ Conjugated linoleic acid significantly increases adiponectin levels, improving insulin resistance and promoting fatty acid oxidation during hyperlipidemia regulation in mice. This effect is accompanied by enhanced expression of phosphorylated protein kinase B/protein kinase B (p-AKT/AKT) and glucose transporter type 2 (GLUT-2). Liver transcriptome analysis revealed alterations in insulin signaling-related genes, including hexokinase 2, suppressor of cytokine signaling 3, nuclear receptor subfamily 4 group A member 1, integrin subunit alpha 5, activating transcription factor 4, colony stimulating factor 1, and eukaryotic translation initiation factor 4E binding protein 1 (HK2, SOCS3, NR4A1, ITGA5, ATF4, CSF1, and EIF4EBP1).³⁷

Relieving inflammation and oxidative stress. Dyslipidemia is closely associated with inflammatory responses and oxidative stress. Excessive inflammatory factors and oxidative free radicals promote the oxidation and modification of LDL, exacerbating dyslipidemia. Therefore, regulating inflammation and oxidative balance is an effective strategy for AFBCs to exert indirect hypolipidemic effects (Fig. 3). Inflammation regulation by AFBCs typically involves the activation of relevant receptors and pathways, modulation of immune cell differentiation, and regulation of cytokine production. Carnosine has been shown to regulate lipids by activating the active substance neuregulin 4 (Nrg4) in brown adipocytes, inhibiting the NLR family pyrin domain containing 3 (NLRP3) and the classical nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) inflammatory pathway.⁷ Carnosine also promotes autophagy to suppress NLRP3 and upregulates the expression of apoptosis-associated speck-like protein containing a CARD, arginase 1, and cluster of differentiation 163 and 206 (ASC, Arg-1, CD163, and CD206), markers that promote M2 macrophage polarization, facilitating cholesterol transport and fatty acid oxidation.⁹⁷ Conjugated linoleic acid significantly reduces the expression of pro-inflammatory macrophage activation markers such as F4/80 and inflammation-related signaling molecules, including phosphorylated C-Jun N-terminal kinase/C-Jun N-terminal kinase (p-JNK/JNK) and phosphorylated inhibitor of nuclear factor kappa-light-chain-enhancer of activated B cells α/inhibitor of nuclear factor kappa-light-chain-enhancer of activated B cells α (p-IκBα/IκBα). Additionally, inflammatory-related pathways, including mitogen-activated protein kinases (MAPK), NF-κB, Toll-like receptors, and hypoxia-inducible factor 1 (HIF-1), are downregulated, as revealed by signal pathway enrichment.³⁷ The egg protein peptide showed a down-regulation effect on inflammatory factors tumor necrosis factor alpha, interleukin-6 and 1 beta (TNF-α, IL-6, and IL-1β) when it was involved in reducing triglyceride synthesis.⁷⁷

Regarding oxidative stress regulation, a cross-sectional study has shown a significant association between an increased dietary antioxidant index and a reduced risk of hyperlipidemia.⁹⁸ AFBCs often exert their hypolipidemic effects through antioxidant properties, such as promoting antioxidant enzyme activity and activating antioxidant signaling pathways. Structural lipids have been found to significantly enhance the levels of superoxide dismutase, catalase, and glutathione peroxidase (SOD, CAT, and GSH-px) by 27.39%, 38.33%, and 22.90%, respectively, supporting their hypolipidemic effects.⁴² Poultry protein modulates blood lipid levels by influencing the antioxidant enzyme paraoxonase 1 (PON1) carried by HDL.¹⁵ Blue mussel hydrolysates activate the HO-1/Nrf2 signaling pathway, reducing intracellular reactive oxygen species and inhibiting foam cell formation.⁸¹ Monkfish swim bladder peptides improve lipid accumulation and oxidative stress in HepG2 cells by activating the AMPK/Nrf2 signaling pathway.⁹⁹ Other common pathways regulating oxidative stress include MAPK, phosphoinositide 3-kinase (PI3K), forkhead box O (FOXO), AMPK, and PPAR, highlighting their close involvement in blood lipid regulation. In addition, studies have shown that there is a correlation between amino acid metabolism and the antioxidant signaling pathway Nrf2.¹⁰⁰ Given the critical role of amino acid metabolism in the hypolipidemic effect, future research on its specific connection will help reveal deeper mechanisms.

The prospect of bioactive compounds from animal-derived foods in the hypolipidemic effect

A systematic summary of the extraction methods, hypolipidemic properties, and underlying mechanisms of AFBCs in current research not only highlights the substantial potential of animal-derived food resources in discovering hypolipidemic active substances but also identifies existing challenges in the field. This section discusses future research directions focusing on broadening sources, optimizing efficiency forms, deepening mechanism exploration, and promoting clinical research (Fig. 4), thereby providing a foundation for the future application of AFBCs in the development of targeted hypolipidemic products.

Fig. 4 The prospect of AFBCs in hypolipidemic activity.

Broadening sources through by-product utilization and virtual screening

The discovery of additional AFBCs with hypolipidemic activity through expanded sourcing is essential for further progress in this field. Animal-derived food processing generates a significant amount of by-products, which, from an environmental and resource perspective, are increasingly seen as valuable sources for extracting bioactive substances. As previously mentioned, it can be seen that glycosaminoglycans⁵⁶ extracted from fish heads, as well as egg crude-chalaza hydrolysates,⁸² have demonstrated effective hypolipidemic properties. Some by-products that have not been noticed in the past may also contain abundant resources, such as blood and bones during the processing of livestock products. Hemoglobin in pig blood plays a role in promoting lipid excretion.¹⁰¹ Sheep bone collagen peptide can alleviate liver lipid deposition in rats.¹⁰² These examples undoubtedly provide directions for subsequent research. With advancements in extraction technology, the application of various new techniques has facilitated the discovery of AFBCs. The review by Ghaffari-Bohlouli et al. emphasizes the promising potential for the high-value utilization of active compounds derived from animal processing by-products, particularly in protein extraction, characterization, and application.¹⁰³ However, several challenges remain in the exploration of hypolipidemic bioactive compounds from animal-derived processing by-products, such as the optimization of extraction methods and functional evaluations. Extraction methods must balance efficiency and purity while also considering factors such as time, cost, and scalability for industrial production. Future research should focus on cost-effective, environmentally sustainable technologies to enhance the value of these by-products. Additionally, safety evaluations and consumer acceptance of bioactive compounds derived from processing by-products should be prioritized in future studies. Furthermore, time-saving and efficient virtual screening methods have begun to play a role in source expansion. For instance, Glide SP (standard precision-peptide method) can be employed to identify bioactive peptides with cholesterol esterase and pancreatic lipase inhibition based on sequence analysis.²⁰ In the evaluation of bioactive peptides with hypolipidemic potential in various fermented milk products, computer simulation technologies not only facilitate the screening process but also predict peptide bioavailability.⁵ The integration of machine learning and artificial intelligence has further advanced the screening of bioactive compounds. Unlike traditional algorithm models, these technologies can autonomously extract molecular features, significantly enhancing prediction accuracy and reliability.¹⁰⁴ Future research should focus on the use of efficient screening models coupled with experimental validation to further broaden the sources of AFBCs.

Optimizing efficiency through composite and delivery systems

The recognition of the food matrix effect has prompted researchers to appreciate the significance of interactions when bioactive compounds exert their effects. As a result, composite systems are increasingly employed to identify optimal hypolipidemic combinations that enhance efficiency. These formulations form the foundation for developing functional foods. For example, when astragalus alcohol was combined with lecithin, it transformed into an irregular form within the matrix, forming a new phase that contributed to its hypolipidemic effects.¹⁰⁵ The bile acid-binding capacity of a 1 : 2 ratio of whey protein to Plantago dietary fiber was three times greater than that of Plantago dietary fiber alone.¹⁰⁶ In addition to the binary system, the milk protein–polyphenol–saccharide ternary complex also plays a role in improving health functions.¹⁰⁷ It can be seen that the synergistic effect of hypolipidemic combinations may be due to the presence of the new substance, the enhancement of physical properties, or the improvement of the bioavailability of the substance. However, the selection criteria of compound combinations and the underlying principles of synergistic effects remain unclear. Moreover, the combination of AFBCs is mostly focused on functional lipids, and there are still few related studies on other substances. In future combination strategies, on the one hand, known effective hypolipidemic bioactive compounds, such as octacosanol, phytosterols, β-glucans, and bergamot polyphenols, can be combined with AFBCs.^108,109 On the other hand, more attention can be paid to some components which have not been fully applied, such as new resource food components, health food components, medicinal and edible homologous components and some nutritional fortifiers. In the process of combination, the modification of active substances by chemical or physical reactions is undoubtedly an effective means, such as glycosylation. Glycosylated substances with hypolipidemic effects, such as glycomacropeptides and lactoferrin, were also naturally present in animal-derived foods. A recent study also showed that glycosylation modification can enhance the pancreatic lipase inhibition of active substances.¹¹⁰ It fully demonstrates the possibility of using glycosylation modified AFBCs to enhance the hypolipidemic effect. The presence of amino sugars in animal cartilage are also a suitable donor for glycosylation modification, so more attention could be paid to this aspect in future research. At the same time, the synergistic effect between AFBCs and other substances, the matrix interactions and how to construct and evaluate more effective and safe composite systems are also future research directions. Furthermore, developing delivery systems using animal-sourced components is an effective strategy to improve bioavailability, biocompatibility, and targeting. A recent study demonstrated a platelet membrane selenium nanoparticle delivery system using chitosan as a modifier, encapsulating miR-148A-3P inhibitors to achieve targeted treatment for hyperlipidemia.¹¹¹ Similarly, collagen peptide-modified nano-selenium has been shown to enhance bile acid binding, exerting a hypolipidemic effect.¹¹² Whey protein, lecithin, and glycosaminoglycan are also common AFBCs used in the construction of delivery systems. In the future, constructing more efficient delivery systems based on AFBCs, such as Pickering emulsions, liposomes, and nanoparticles, will be essential. Based on the discussion in the previous section, it is known that some phospholipids can participate in the lipid distribution of the cell membrane. Glycosaminoglycans, as an important part of the cell matrix, can also bind to some receptors. Whether the properties of these substances can effectively improve the targeting of active substances is also a matter of concern. Additionally, safety evaluations of these delivery systems and the refinement of corresponding regulatory frameworks will be crucial for their development.

Deepening mechanism exploration via target and biomarker identification

In-depth exploration of mechanisms is essential for advancing the application of bioactive compounds. The hypolipidemic effects of animal-derived active ingredients are often linked to multiple targets, with cross-interactions between these targets. Modern computational technologies not only facilitate the broadening of sources but also provide a fresh perspective on mechanism analysis. Using network pharmacology, 64 potential targets of fish oil fatty acids in the synergistic anti-hyperlipidemic effect have been identified.¹¹³ In studying the hypolipidemic mechanism of chitobiose, molecular docking revealed that its cumulative metabolite, butyric acid, forms hydrogen bonds with the hydrophilic ligand binding domain of PPARα, thereby activating it.⁶⁸ However, target prediction is primarily based on existing data models, which may limit the discovery of new hypolipidemic targets. To overcome this, future research should focus on expanding databases related to the structural characteristics of animal-derived hypolipidemic bioactive compounds and incorporating other relevant target data, thereby facilitating the identification of novel targets. Advances in modern technology may facilitate the discovery of natural inhibitors from animal-derived foods, which could effectively suppress fat absorption and accumulation. Moreover, biomarkers play a critical role in reflecting key changes during the hypolipidemic effects of AFBCs. Biomarkers, detectable substances that appear after target activation, are vital for disease regulation and diagnosis. Their discovery is closely linked to the application of multi-omics approaches, including metabolomics, proteomics, transcriptomics, and metagenomics. With research advances, more and more characteristic microbiota related to hyperlipidemia have been identified.¹¹⁴ However, the influence of different AFBCs on these characteristic microbiota requires further investigation. Future studies should focus on the impact of AFBCs on microbiota combination and the interaction between compounds and the microbiota, incorporating the concept of “species interaction groups” and specific enzyme genes encoded by the gut microbiota.¹¹⁵ Additionally, in terms of metabolic markers, the use of isotope tracking markers and metabolic flow platforms will help identify metabolic markers and clarify metabolic distribution.¹¹⁶ Furthermore, numerous studies have indicated that various microRNAs are involved in blood lipid regulation, suggesting their potential as biomarkers.¹¹⁷ Astaxanthin can affect miR-3073b-5p to promote cholesterol efflux during regulation.⁹ For example, astaxanthin can influence miR-3073b-5p to promote cholesterol efflux during regulation. However, the relationship between the hypolipidemic effects of animal-derived dietary components and microRNA, as well as the potential of microRNAs as stable biomarkers, requires further exploration.

Promoting clinical research to provide more scientific evidence

Currently, most evaluations of the hypolipidemic activity of AFBCs rely on in vitro biochemical experiments, cellular models, or rodent studies. While these models contribute to functional evaluations, they do not accurately replicate the complex biological metabolism in humans. Consequently, hypolipidemic bioactive compounds that show effectiveness in animal studies may not exhibit the same results in clinical trials.¹¹⁸ Therefore, advancing clinical research is crucial to provide robust scientific evidence supporting the hypolipidemic effects of AFBCs. In some existing clinical studies, ABFC intake mainly includes direct intake, addition to the food matrix, or preparation into capsules. Whether different forms of supplementation will bring differences is an aspect to be considered in the follow-up research. At the same time, the use of AFBCs as the main ingredient to form products for clinical research may also be a direction in the future. The individual differences within populations, the complexity of in vivo metabolism, and the influence of various confounding factors present significant challenges to clinical validation. A recent study predicting the effects of long-term milk fat intake on LDL-C and HDL-C levels in mice, both on normal and high-fat diets, highlighted that individual core factors and their interrelationships have a common impact on blood lipids.¹¹⁹ This finding suggests that, in clinical studies, it is important to consider individual factors and their relationship with the regularity of AFBCs’ hypolipidemic effects, including tracking blood biochemical markers, assessing physiological changes, and understanding the temporal effects of AFBC intake. Additionally, it would be valuable to explore whether the impact of AFBCs differs in individuals with hyperlipidemia accompanied by other diseases, and large-scale population cohort studies are necessary in this field. Furthermore, the development of predictive models plays a critical role in clinical research. Microbial community metabolic models can predict individual-specific changes in SCFA production,¹²⁰ while the concept of “precise calories” offers a framework for fine-tuning energy control and dynamic adjustment.¹²¹ Although these new approaches have not yet been fully implemented, advancements in science and technology, combined with the growing body of research, offer increased potential for creating universal and accurate prediction models. In parallel, the establishment of a comprehensive data platform that integrates population genomics, epidemiological data, and predictive models will further accelerate the clinical evaluation of AFBCs in the future.

Conclusions

This review offers an in-depth analysis of extraction methods, hypolipidemic properties, and molecular mechanisms of AFBCs, drawing on the latest research in animal-derived food resource utilization for hypolipidemic bioactivity. The application of advanced technology and compound extraction technology is conducive to the mining of bioactive compounds. These AFBCs demonstrate a broad spectrum of hypolipidemic effects and engage with multiple targets. Future research should prioritize the high-value utilization of by-products and virtual screening to expand sources, the development of composite and delivery systems to optimize efficacy, and the identification of targets and biomarkers to deepen mechanistic understanding. Additionally, advancing clinical research is essential to provide stronger scientific evidence. By integrating comprehensive data sources, the progress of precision nutrition can be achieved, facilitating the valorization of animal-derived foods and supporting the development of targeted hypolipidemic products.

Author contributions

Jieying Ou: conceptualization, methodology, investigation, and writing – original draft. Yuzhuo Wang: writing – reviewing & editing and conceptualization. Yuxin Li: writing – reviewing & editing and formal analysis. Simiao Liu: writing – reviewing & editing and software. XinFang Kou: software and formal analysis. Fazheng Ren: formal analysis and supervision. Xuemei Wang: writing – reviewing & editing, supervision, and funding acquisition. Hao Zhang: supervision, project administration, and funding acquisition.

Conflicts of interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Abbreviations

AFBCs	Animal food bioactive compounds
TC	Total cholesterol
TG	Total triglyceride
HDL	High-density lipoprotein
LDL	Low-density lipoprotein
PUFAs	Polyunsaturated fatty acids
MLCT	Medium- and long-chain triacylglycerols
OPO	1,3-Dioleoyl-2-palmitoylglycerol
DGA	Diacylglycerol
GSP	Glycated serum protein
GLU	Glucose
AST	Aspartate aminotransferase
ALT	Alanine aminotransferase
ALP	Alkaline phosphatase
LDH	Lactate dehydrogenase
GGT	Gamma-glutamyl transferase
NEFAs	Non-esterified fatty acids
INS	Insulin
IL-6	Interleukin-6
IL-1β	Interleukin-1 beta
TNF-α	Tumor necrosis factor alpha
IL-10	Interleukin-10
CRI	Cholesterol retention index
AI	Atherogenic index
HOMA-IA	Homeostatic model assessment of insulin resistance
ApoB-48	Apolipoprotein B-48
PUFAs	Polyunsaturated fatty acids
MLCT	Medium- and long-chain triglycerides
DGA	Diacylglycerol acyltransferase
SPT1	Serine palmitoyltransferase 1
LXR	Liver X receptor
TBXAS1	Thromboxane A synthase 1
CBR3	Carbonyl reductase 3
CCL4	Chemokine (C–C motif) ligand 4
CCL2	Chemokine (C–C motif) ligand 2
ADGRE1	Adhesion G protein-coupled receptor E1
LAMP1	Lysosomal-associated membrane protein 1
MTP	Microsomal triglyceride transfer protein
ACSL1	Acyl-CoA synthetase long-chain family member 1
PL	Pancreatic lipase
CE	Cholesterol esterase
NPC1L1	Niemann-Pick C1-like 1
FAP2	Fatty acid-binding protein 2
FAP4	Fatty acid-binding protein 4
L-FABP	Liver fatty acid-binding protein
GPD1	Glycerol-3-phosphate dehydrogenase 1
DGAT1	Diacylglycerol acyltransferase 1
DGAT2	Diacylglycerol acyltransferase 2
FAS	Fatty acid synthase
ACL	ATP-citrate lyase
ACC	Acetyl-CoA carboxylase
Acaca	Acetyl-CoA carboxylase α
SCD	Stearoyl-CoA desaturase
PDK	Pyruvate dehydrogenase kinase
SREBP-1	Sterol regulatory element-binding protein 1
C/EBP-α	CCAAT/enhancer-binding protein alpha
PPARγ	Peroxisome proliferator-activated receptor gamma
AMPK	AMP-activated protein kinase
FXR	Farnesoid X receptor
PPARα	Peroxisome proliferator-activated receptor alpha
HSL	Hormone-sensitive lipase
ATGL	Adipose triglyceride lipase
CPT1A	Carnitine palmitoyltransferase 1A
CPT2	Carnitine palmitoyltransferase 2
UCP	Uncoupling protein
PGC-1α	Peroxisome proliferator-activated receptor gamma coactivator 1-alpha
HNF1α	Hepatocyte nuclear factor 1 alpha
HNF4α	Hepatocyte nuclear factor 4 alpha
LDLR	Low-density lipoprotein receptor
SR-A1	Scavenger receptor class A type 1
CD36	Cluster of differentiation 36
SR-BI	Scavenger receptor class B type 1
PCSK9	Proprotein convertase subtilisin/kexin type 9
HMGCR	3-Hydroxy-3-methylglutaryl-CoA reductase
SQLE	Squalene epoxidase
SQS	Squalene synthase
SMYD3	SET and MYND domain containing 3
SREBP2	Sterol regulatory element-binding protein 2
SCD1	Stearoyl-CoA desaturase 1
ACAT2	Acetyl-CoA acetyltransferase 2
LCAT	Lecithin-cholesterol acyltransferase
ABCG5	ATP-binding cassette subfamily G member 5
ABCG8	ATP-binding cassette subfamily G member 8
ABCA1	ATP-binding cassette subfamily A member 1
ABCG1	ATP-binding cassette subfamily G member 1
ERK	Extracellular signal-regulated kinase
LXRα	Liver X receptor alpha
CYP7A1	Cytochrome P450 family 7 subfamily A member 1
CYP27A1	Cytochrome P450 family 27 subfamily A member 1
CYP2C70	Cytochrome P450 family 2 subfamily C member 70
CYP8B1	Cytochrome P450 family 8 subfamily B member 1
CYP7B1	Cytochrome P450 family 7 subfamily B member 1
FGF19	Fibroblast growth factor 19
ABCB11	ATP-binding cassette subfamily B member 11
OATP2	Organic anion transporting polypeptide 2
BHMT	Betaine-homocysteine S-methyltransferase
BACS	Bile acid-CoA synthase
BSEP	Bile salt export pump
NTCP	Sodium/taurocholate cotransporting polypeptide
GLP-1	Glucagon-like peptide-1
GLUT-4	Glucose transporter type 4
GLUT-2	Glucose transporter type 2
PI3K	Phosphoinositide 3-kinase
Akt	Protein kinase B
HK2	Hexokinase 2
SOCS3	Suppressor of cytokine signaling 3
NR4A1	Nuclear receptor subfamily 4 group A member 1
ITGA5	Integrin subunit alpha 5
ATF4	Activating transcription factor 4
CSF1	Colony stimulating factor 1
EIF4EBP1	Eukaryotic translation initiation factor 4E binding protein 1
Nrg4	Neuregulin 4
NLRP3	NLR family pyrin domain containing 3
NF-κB	Nuclear factor kappa-light-chain-enhancer of activated B cells
ASC	Apoptosis-associated speck-like protein containing a CARD
Arg-1	Arginase 1
CD163	Cluster of differentiation 163
CD206	Cluster of differentiation 206
MAPK	Mitogen-activated protein kinases
HIF-1	Hypoxia-inducible factor 1
SOD	Superoxide dismutase
CAT	Catalase
GSH-Px	Glutathione peroxidase
PON1	Paraoxonase 1
JNK	c-Jun N-terminal kinase
Nrf2	Nuclear factor erythroid 2-related factor 2
PI3K	Phosphoinositide 3-kinase
FOXO	Forkhead box O
GK	Glucokinase
GSK3β	Glycogen synthase kinase 3
G6Pase	Glucose-6-phosphatase
PEPCK1	Phosphoenolpyruvate carboxykinase 1
GLP-1	Glucagon-like peptide-1

Data availability

No primary research results, software or code have been included and no new data were generated or analysed as part of this review.

Acknowledgements

This work was supported by the National Key R&D Program of China (2024YFD2101002) and the 2115 Talent Development Program of China Agricultural University.

References

1. A. Pirillo, M. Casula, E. Olmastroni, G. D. Norata and A. L. Catapano, Global epidemiology of dyslipidaemias, Nat. Rev. Cardiol., 2021, 18, 689–700.
2. M. Alwahsh, R. Alejel, A. Hasan, H. Abuzaid and T. Al-Qirim, The Application of Metabolomics in Hyperlipidemia: Insights into Biomarker Discovery and Treatment Efficacy Assessment, Metabolites, 2024, 14, 438.
3. S. Sheffield, M. Fiorotto and T. Davis, Nutritional importance of animal-sourced foods in a healthy diet, Front. Nutr., 2024, 11, 1424912.
4. M. Li, X. Jia, Q. Yao, F. Zhu, Y. Huang and X. Zeng, Recent advance for animal-derived polysaccharides in nanomaterials, Food Chem., 2024, 459, 140208.
5. P. Mudgil, A. Redha, N. Nirmal and S. Maqsood, In vitro antidiabetic and antihypercholesterolemic activities of camel milk protein hydrolysates derived upon simulated gastrointestinal digestion of milk from different camel breeds, J. Dairy Sci., 2023, 106, 3098–3108.
6. S. Yang, X. C. Wang, H. Li, X. X. Wang, Y. Song, P. X. Cong, J. Xu and C. H. Xue, Sea Cucumber Phospholipids Regulate Cholesterol Metabolism in High-Fat Diet-Induced ApoE^−/− Mice, J. Nutr., 2023, 153, 1762–1770.
7. J. Luo, M. Chen, H. Ji, W. Su, W. Song, D. Zhang, W. Su and S. Liu, Brown adipose tissue-derived Nrg4 alleviates non-alcoholic fatty liver disease in mice, J. Funct. Foods, 2023, 108, 105735.
8. X. Guo, T. Ou, X. Yang, Q. Song, L. Zhu, S. Mi, J. Zhang, Y. Zhang, W. Chen and J. Guo, Untargeted metabolomics based on ultra-high performance liquid chromatography-mass spectrometry/MS reveals the lipid-lowering mechanism of taurine in hyperlipidemia mice, Front. Nutr., 2024, 11, 1367589.
9. Z. Zhang, Y. Qiu, W. Li, A. Tang, H. Huang, W. Yao, H. Li and T. Zou, Astaxanthin Alleviates Foam Cell Formation and Promotes Cholesterol Efflux in Ox-LDL-Induced RAW264.7 Cells via CircTPP2/miR-3073b-5p/ABCA1 Pathway, Molecules, 2023, 28, 1701.
10. Y. J. Zhou, J. M. Liang, Y. Zhang, H. J. Zhang, S. K. C. Chang, H. Hong, Y. K. Luo and Y. Q. Tan, Silver carp swim bladder collagen derived from deep eutectic solvents: Enhanced solubility against pH and NaCl stresses, Int. J. Biol. Macromol., 2024, 281, 136315.
11. L. Andrade, E. Guilherme, A. Hijo, C. Bruziquesi, I. Brandi, W. J. Lima, G. de Carvalho and B. Mesquita, Capturing whey proteins from milk whey using an ionic liquid-based magnetic adsorbent, Innovative Food Sci. Emerging Technol., 2025, 100, 103914.
12. F. Wang, D. Shu, Y. Wei, X. Guo, P. Liu, X. Deng, Y. Zhao, Y. Lei and J. Zhang, Effect of Ultrasonic Intensity Treatment on the Physicochemical and Functional Properties of Coregonus peled Protamine, Foods, 2025, 14, 481.
13. R. Ortizo, V. Sharma, M. Tsai, P. Nargotra, P. Sun, C. Chen and C. Dong, A novel deep eutectic solvent-based green extraction and purification of DPP-IV inhibitory peptides from tilapia (Oreochromis niloticus) viscera hydrolysate, Food Biosci., 2024, 61, 104658.
14. L. Day, J. Cakebread and S. Loveday, Food proteins from animals and plants: Differences in the nutritional and functional properties, Trends Food Sci. Technol., 2022, 119, 428–442.
15. R. Martínez-Beamonte, J. Sánchez-Marco, M. Gómez, G. Lázaro, M. Barco, T. Herrero-Continente, M. Serrano-Megías, D. Botaya, C. Arnal, C. Barranquero, J. Surra, J. Manso-Alonso, J. Osada and M. Navarro, Dietary proteins modulate high-density lipoprotein characteristics in a sex-specific way in Apoe-deficient mice, Nutrition, 2023, 116, 112211.
16. S. Jiang, S. Ji, X. Tang, T. Wang, H. Wang and X. Meng, A Comparison Study on the Therapeutic Effect of High Protein Diets Based on Pork Protein versus Soybean Protein on Obese Mice, Foods, 2022, 11, 1227.
17. M. Ding, Z. Huang, Z. Huang, Z. Zhao, D. Zhao, K. Shan, W. Ke, M. Zhang, G. Zhou and C. Li, Proteins from different sources in a high-fat food matrix influence lipid hydrolysis through bolus coalescence and interactions with bile salts, Food Hydrocolloids, 2023, 141, 108748.
18. X. Shi, Z. Huang, G. Zhou and C. Li, Dietary Protein From Different Sources Exerted a Great Impact on Lipid Metabolism and Mitochondrial Oxidative Phosphorylation in Rat Liver, Front. Nutr., 2021, 8, 719144.
19. C. Liu, Y. Wu, G. Jin, B. Xu and L. Mei, Structural modifications and augmented affinity for bile salts in enzymatically denatured egg white, Food Chem.:X, 2024, 23, 101577.
20. Z. Zhang, S. Jiang, Y. Li, D. Xie and J. Li, Residue profiles of peptides with cholesterol esterase and pancreatic lipase inhibitory activities through virtual screening and sequence analysis, Food Chem., 2024, 460, 140708.
21. K. Wang, L. Han, Y. Tan, H. Hong, H. Fan and Y. Luo, Novel Hypocholesterolemic Peptides Derived from Silver Carp Muscle: The Modulatory Effects on Enterohepatic Cholesterol Metabolism In Vitro and In Vivo, J. Agric. Food Chem., 2023, 71, 5565–5575.
22. Y. Song, Q. Cai, S. Wang, L. Li, Y. Wang, S. Zou, X. Gao and Y. Wei, The Ameliorative Effect and Mechanisms of Ruditapes philippinarum Bioactive Peptides on Obesity and Hyperlipidemia Induced by a High-Fat Diet in Mice, Nutrients, 2022, 14, 5066.
23. F. Wu, Z. Wang, X. Song, M. Yang, Y. Xu, X. Zeng, Z. Wu, D. Pan, H. Luo, L. Lv and Y. Guo, The cholesterol-lowering effects and mechanisms of novel milk casein-derived peptides in hyperlipidemia and hypercholesterol mice, Food Biosci., 2024, 61, 104730.
24. Y. Zhang, T. Zhang, Y. Liang, L. Jiang and X. Sui, Dietary Bioactive Lipids: A Review on Absorption, Metabolism, and Health Properties, J. Agric. Food Chem., 2021, 69, 8929–8943.
25. R. Saini, P. Prasad, X. Shang and Y. Keum, Advances in Lipid Extraction Methods-A Review, Int. J. Mol. Sci., 2021, 22, 13643.
26. Y. Liu, Y. Li, W. Yu, Y. Ma, Y. Cao and L. Zhao, Extraction of high-quality Antarctic krill (Euphausia Superba) oil using low-temperature continuous phase-transition extraction equipment, J. Food Sci., 2024, 89, 9073–9087.
27. J. Tu, S. Liu, Y. Liang, X. Guo, C. Brennan, X. Dong and B. Zhu, A novel micro-aqueous cold extraction of salmon head oil to reduce lipid oxidation and fishy odor: Comparison with common methods, Food Chem., 2025, 463, 141260.
28. T. Mai, Y. Choi, H. Park, J. Cheon, J. Choi, D. Park and H. Kim, Green ultrasound-assisted extraction of fish oil from rainbow trout intestines and purification with adsorbents, Appl. Biol. Chem., 2023, 66, 80.
29. X. Zou, I. Khan, Y. Wang, M. Hussain, B. Jiang, L. Zheng, Y. Pan, J. Hu and M. Khalid, Preparation of medium- and long-chain triacylglycerols rich in n-3 polyunsaturated fatty acids by bio-imprinted lipase-catalyzed interesterification, Food Chem., 2024, 455, 139907.
30. B. Wang, M. Zhang, W. Ge, K. He and F. Cheng, Microencapsulated duck oil diacylglycerol: Preparation and application as anti-obesity agent, LWT – Food Sci. Technol., 2019, 101, 646–652.
31. Y. Chooi, Q. Zhang, F. Magkos, M. Ng, N. Michael, X. Wu, V. Volchanskaya, X. Lai, E. Wanjaya, U. Elejalde, C. Chan, C. Yap, L. Wong, K. Lim, S. Velan, J. Yaligar, M. Muthiah, Y. Chong, E. Loo and J. Eriksson, Effect of an Asian-adapted Mediterranean diet and pentadecanoic acid on fatty liver disease: the TANGO randomized controlled trial, Am. J. Clin. Nutr., 2024, 119, 788–799.
32. J. Wang, S. Zheng, Z. Li, Y. Tang, Y. Huang, J. Wang, R. Li and J. Peng, Pentadecanoic acid (C15:0, PA) induces mild maternal glucose intolerance and promotes the growth of the offspring partly through up-regulating liver PPARα and MAPK signaling pathways, Food Funct., 2024, 15, 11400–11414.
33. J. Zheng, S. Sharp and F. Imamura, et al., Association between plasma phospholipid saturated fatty acids and metabolic markers of lipid, hepatic, inflammation and glycaemic pathways in eight European countries: a cross-sectional analysis in the EPIC-InterAct study, BMC Med., 2017, 15, 203.
34. Y. Chen, Z. Fan, X. Gao, F. Zhou, X. Guo, A. Sinclair and D. Li, n-3 polyunsaturated fatty acids in phospholipid or triacylglycerol form attenuate nonalcoholic fatty liver disease via mediating cannabinoid receptor 1/adiponectin/ceramide pathway, J. Nutr. Biochem., 2024, 123, 109484.
35. S. Hwang, Y. Kim, J. Kim, Y. Chun, Y. Kwon, S. Ku and C. Song, Preventive and Therapeutic Effects of Krill Oil on Obesity and Obesity-Induced Metabolic Syndromes in High-Fat Diet-Fed Mice, Mar. Drugs, 2022, 20, 483.
36. N. Azemi, A. Azemi, L. Abu-Bakar, V. Sevakumaran, T. Muhammad and N. Ismail, Xestospongia muta Fraction-7 and Linoleic Acid: Effects on SR-BI Gene Expression and HDL Cholesterol Uptake, Mar. Drugs, 2022, 20, 762.
37. L. Wu, S. Ye, X. Deng, Z. Fu, J. Li and C. Yang, Conjugated Linoleic Acid Ameliorates High Fat-Induced Insulin Resistance via Regulating Gut Microbiota-Host Metabolic and Immunomodulatory Interactions, Nutrients, 2024, 16, 1133.
38. Y. Yang, Y. Xia, B. Zhang, D. Li, J. Yan, J. Yang, J. Sun, H. Cao, Y. Wang and F. Zhang, Effects of different n-6/n-3 polyunsaturated fatty acids ratios on lipid metabolism in patients with hyperlipidemia: a randomized controlled clinical trial, Front. Nutr., 2023, 10, 1166702.
39. V. Zammit and S. Park, In Vivo Monitoring of Glycerolipid Metabolism in Animal Nutrition Biomodel-Fed Smart-Farm Eggs, Foods, 2024, 13, 722.
40. Z. Yu, C. Liu, Y. Gao, H. Guo, H. Duan, L. Zhang and Y. Chen, Insight into effects of egg- and soybean-derived phosphatidylcholine on non-alcoholic steatosis in mice and HepG2 cells by lipidomics, Food Sci. Hum. Wellness, 2025, 14, 9250103.
41. C. Millar, C. Jiang, G. Norris, C. Garcia, S. Seibel, L. Anto, J. Lee and C. Blesso, Cow's milk polar lipids reduce atherogenic lipoprotein cholesterol, modulate gut microbiota and attenuate atherosclerosis development in LDL-receptor knockout mice fed a Western-type diet, J. Nutr. Biochem., 2020, 79, 108351.
42. Y. Huang, N. Wang and H. Zhao, In vivo activities of the structured lipids-1, 3-dioleic acid 2-palmitic acid triglyceride (OPO) in high-fat diet mice, Food Biosci., 2022, 47, 101667.
43. S. Paul, A. Smith, K. Culham, K. Gunawan, J. Weir, M. Cinel, K. Jayawardana, N. Mellett, M. Lee, A. Murphy, G. Lancaster, P. Nestel, B. Kingwell and P. Meikle, Shark liver oil supplementation enriches endogenous plasmalogens and reduces markers of dyslipidemia and inflammation, J. Lipid Res., 2021, 62, 100092.
44. X. Guan, F. Wang, B. Zhou, X. Sang and Q. Zhao, The nutritional function of active polysaccharides from marine animals: A review, Food Biosci., 2024, 58, 103693.
45. B. Yang, C. Yang, R. Liu, W. Sui, Q. Zhu, Y. Jin, T. Wu and M. Zhang, The Relationship between Preparation and Biological Activities of Animal-Derived Polysaccharides: A Comprehensive Review, Foods, 2024, 13, 173.
46. M. Tsai, C. Huang, P. Nargotra, W. Tang, K. Liao, Y. Lee, C. Lin, C. Lin, C. Shieh and C. Kuo, Green extraction and purification of chondroitin sulfate from jumbo squid cartilage by a novel procedure combined with enzyme, ultrasound and hollow fiber dialysis, J. Food Sci. Technol., 2023, 60, 1711–1722.
47. A. Tarannum, S. Ballav, J. Rao and N. Fathima, Extraction of dermatan sulfate using ionic liquid-assisted enzymatic digestion: An efficient approach, Carbohydr. Res., 2023, 531, 108897.
48. X. Tan, X. Wang, F. Cui, A. Zeshan, D. Wang, X. Li and J. Li, Effect of Enterococcus hirae GS22 Fermentation-Assisted Extraction on the Physicochemical and Bioactivities of Sea Cucumber Intestinal Polysaccharides, Molecules, 2024, 29, 5800.
49. D. Yin, Y. Zhong, H. Liu and J. Hu, Lipid metabolism regulation by dietary polysaccharides with different structural properties, Int. J. Biol. Macromol., 2024, 270, 132253.
50. R. Gao, Z. Qi, J. Lin, G. Wang, G. Chen, L. Yuan and Q. Sun, Chondroitin Sulfate Alleviated Obesity by Modulating Gut Microbiota and Liver Metabolome in High-Fat-Diet-Induced Obese Mice, J. Agric. Food Chem., 2023, 71, 9419–9428.
51. C. Rai, C. Nandini and P. Priyadarshini, Composition and structure elucidation of bovine milk glycosaminoglycans and their anti-adipogenic activity via modulation PPAR-γ and C/EBP-α, Int. J. Biol. Macromol., 2021, 193, 137–144.
52. S. Li, R. Guo, X. Gao, Y. Wang, J. Wen, T. Zhao, X. Guo, J. Li, S. Chen and D. Li, Fucosylated chondroitin sulfate alleviates diet-induced obesity by modulating intestinal lipid metabolism and colonic microflora, Int. J. Biol. Macromol., 2024, 283, 137371.
53. S. Li, J. Li, Z. Zhi, C. Wei, W. Wang, T. Ding, X. Ye, Y. Hu, R. Linhardt and S. Chen, Macromolecular properties and hypolipidemic effects of four sulfated polysaccharides from sea cucumbers, Carbohydr. Polym., 2017, 173, 330–337.
54. P. Qiu, A. Xia, X. Yang, L. Yi, Y. Ouyang, Y. Yao, H. Liu, L. Li and Z. Zhang, Metabolomic analysis reveals the potential of fucosylated chondroitin sulfate from sea cucumber in modulating metabolic homeostasis, J. Pharm. Biomed. Anal., 2025, 252, 116509.
55. Z. Liu, Y. Zhang, C. Ai, W. Tian, C. Wen, S. Song and B. Zhu, An acidic polysaccharide from Patinopecten yessoensis skirt prevents obesity and improves gut microbiota and metabolism of mice induced by high-fat diet, Food Res. Int., 2022, 154, 110980.
56. V. Geetha, M. Das, M. Zarei, V. Mayookha, N. Harohally and G. Kumar, Studies on the partial characterization of extracted glycosaminoglycans from fish waste and its potentiality in modulating obesity through in vitro and in vivo, Glycoconjugate J., 2022, 39, 525–542.
57. B. Stojnic, S. Galmés, A. Serrano, M. Sulli, L. Susak, N. Seye, A. Palou, G. Diretto, M. Bonet and J. Ribot, Glycosaminoglycan dermatan sulfate supplementation decreases diet-induced obesity and metabolic dysfunction in mice, BioFactors, 2024, 50, 493–508.
58. C. Gustafsen, D. Olsen, J. Vilstrup, S. Lund, A. Reinhardt, N. Wellner, T. Larsen, C. Andersen, K. Weyer, J. Li, P. Seeberger, S. Thirup, P. Madsen and S. Glerup, Heparan sulfate proteoglycans present PCSK9 to the LDL receptor, Nat. Commun., 2017, 8, 503.
59. D. Calhoon, L. Sang, F. Ji, D. Bezwada, S. Hsu, F. Cai, N. Kim, A. Basu, R. Wu, A. Pimentel, B. Brooks, K. La, A. Serrano, D. Cassidy, L. Cai, V. Toffessi-Tcheuyap, M. Moussa, W. Uritboonthai, L. Hoang, M. Kolli, B. Jackson, V. Margulis, G. Siuzdak, J. Brugarolas, I. Corbin, D. A. Pratt, R. J. Weiss, R. J. DeBerardinis, K. Birsoy and J. Garcia-Bermudez, Glycosaminoglycan-driven lipoprotein uptake protects tumours from ferroptosis, Nature, 2025, 644(8077), 799–808.
60. S. Ahn, S. Cho and N. Choi, Effectiveness of Chitosan as a Dietary Supplement in Lowering Cholesterol in Murine Models: A Meta-Analysis, Mar. Drugs, 2021, 19, 26.
61. L. Zhang, J. Jiang, W. Liu, L. Wang, Z. Yao, H. Li, J. Gong, C. L. Kang, L. Liu, Z. Xu and J. Shi, Identification and Characterization of a Highly Active Hyaluronan Lyase from Enterobacter asburiae, Mar. Drugs, 2024, 22, 399.
62. W. Tian, Y. You, X. Sun, L. Wang, L. Wang, S. Wang, C. Ai and S. Song, H₂O₂ -TiO₂ photocatalytic degradation of chondroitin sulfate and in vivo absorption and excertion of its product, Carbohydr. Polym., 2023, 301, 120295.
63. S. Liu, R. Chen and M. Chiang, Effects and Mechanisms of Chitosan and ChitosanOligosaccharide on Hepatic Lipogenesis and Lipid Peroxidation, Adipose Lipolysis, and Intestinal Lipid Absorption in Rats with High-Fat Diet-Induced Obesity, Int. J. Mol. Sci., 2021, 22, 1139.
64. M. Zhou, J. Huang, J. Zhou, C. Zhi, Y. Bai, Q. Che, H. Cao, J. Guo and Z. Su, Anti-Obesity Effect and Mechanism of Chitooligosaccharides Were Revealed Based on Lipidomics in Diet-Induced Obese Mice, Molecules, 2023, 28, 5595.
65. Q. Wang, Y. Jiang, X. Luo, C. Wang, N. Wang, H. He, T. Zhang and L. Chen, Chitooligosaccharides Modulate Glucose-Lipid Metabolism by Suppressing SMYD3 Pathways and Regulating Gut Microflora, Mar. Drugs, 2020, 18, 69.
66. A. Abdo, C. Zhang, S. Al-Dalali, Y. Hou, J. Gao, M. Yahya, A. Saleh, H. Aleryani, Z. Al-Zamani and Y. Sang, Marine Chitosan-Oligosaccharide Ameliorated Plasma Cholesterol in Hypercholesterolemic Hamsters by Modifying the Gut Microflora, Bile Acids, and Short-Chain Fatty Acids, Nutrients, 2023, 15, 2923.
67. M. Zhu, W. Zhang, K. Dekyi, L. Zheng, Y. Zhang, Y. Lv and H. Li, Potential effects of sialic acid and 3′-Sialyllactose on intestinal health and anti-cardiovascular disease in mice fed with a high-fat diet, J. Funct. Foods, 2024, 116, 106215.
68. X. Zhuang, M. Zhao, X. Ji, S. Yang, H. Yin and L. Zhao, Chitobiose exhibited a lipid-lowering effect in ob/ob^−/− mice via butyric acid enrolled liver-gut crosstalk, Bioresour. Bioprocess., 2023, 10, 79.
69. A. Haque, J. Park, T. Cong, V. Roy, M. Ali, A. Kiddane, G. Kim and B. Chun, Characterization of oil and amino acids obtained from yellow corvina by-products using subcritical and supercritical fluids, J. Supercrit. Fluids, 2023, 199, 105970.
70. Z. Li, Y. Chen, L. Wu, H. Chen, B. Yang and Y. Wang, Four-liquid-phase system for simultaneous extraction and separation method of various active components in Antarctic krill crude oil extract, Sep. Purif. Technol., 2025, 359, 130415.
71. J. Yang, T. Zhang, Z. Yu, C. Wang, Y. Zhao, Y. Wang and C. Xue, Taurine Alleviates Trimethylamine N -Oxide-Induced Atherosclerosis by Regulating Bile Acid Metabolism in ApoE^−/− Mice, J. Agric. Food Chem., 2022, 70, 5738–5747.
72. A. Prakashan, S. Muthukumar and A. Martin, Taurine Activates SIRT1/AMPK/FOXO1 Signaling Pathways to Favorably Regulate Lipid Metabolism in C57BL6 Obese Mice, Mol. Nutr. Food Res., 2024, 68, 2200660.
73. J. Li, Y. Zhang, S. Yang, Z. Lu, G. Li, S. Wu, D. Wu, J. Liu, B. Zhou, H. Wang and S. Huang, The Beneficial Effects of Edible Kynurenic Acid from Marine Horseshoe Crab (Tachypleus tridentatus) on Obesity, Hyperlipidemia, and Gut Microbiota in High-Fat Diet-Fed Mice, Oxid. Med. Cell. Longevity, 2021, 2021, 8874503.
74. T. Seko, Y. Sato, M. Kuniyoshi, Y. Murata, K. Ishihara, Y. Yamashita, S. Fujiwara, T. Ueda and M. Yamashita, Distribution and Effects of Selenoneine by Ingestion of Extract from Mackerel Processing Residue in Mice, Mar. Biotechnol., 2023, 25, 1020–1030.
75. L. Longhitano, D. Tibullo, T. Zuppelli, S. Ronsisvalle, E. L. Spina, A. Nicolosi, M. Antoci, F. Sipala, F. Galvano, W. Currenti, A. Santisi, A. Alanazi, G. Zanghi, E. Tropea, G. L. Volti and I. A. Barbagallo, (+)Alpha-Lipoic Acid Regulates Lipid Metabolism Gene Expression and Lipidic Profile in a Cellular Model of Fatty Acid Overload, Front. Biosci.-Landmark, 2024, 29, 209.
76. Y. Luan, F. Zhang, Y. Cheng, J. Liu, R. Huang, M. Yan, Y. Wang, Z. He, H. Lai, H. Wang, H. Ying, F. Guo and Q. Zhai, Hemin Improves Insulin Sensitivity and Lipid Metabolism in Cultured Hepatocytes and Mice Fed a High-Fat Diet, Nutrients, 2017, 9, 805.
77. Z. Liu, S. Ding, H. Jiang and J. Fang, Egg Protein Transferrin-Derived Peptides Irw (Lle-Arg-Trp) and Iqw (Lle-Gln-Trp) Prevent Obesity Mouse Model Induced by a High-Fat Diet via Reducing Lipid Deposition and Reprogramming Gut Microbiota, Int. J. Mol. Sci., 2022, 23, 11227.
78. F. Lau and R. Giugliano, Adenosine Triphosphate Citrate Lyase and Fatty Acid Synthesis Inhibition A Narrative Review, JAMA Cardiol., 2023, 8, 879–887.
79. R. Chilakala, H. Moon, M. Jung, J. Han, K. Ko, D. Lee and S. Cheong, Bioactive Peptides from Meretrix lusoria Enzymatic Hydrolysate as a Potential Treatment for Obesity in db/db Mice, Nutrients, 2024, 16, 1913.
80. J. Guo, Y. Wang, P. Li, W. Wu, F. Xu, K. Zhou and B. Xu, The modulatory effects on enterohepatic cholesterol metabolism of novel cholesterol-lowering peptides from gastrointestinal digestion of Xuanwei ham, Food Res. Int., 2023, 173, 113391.
81. C. Marasinghe, S. Yoon and J. Je, Blue mussel (Mytilus edulis) hydrolysates attenuate oxidized-low density lipoproteins (ox-LDL)-induced foam cell formation, inflammation, and oxidative stress in RAW264.7 macrophages, Process Biochem., 2023, 134, 131–140.
82. J. Chen, Y. Lin, Y. Wu, S. Wang, C. Chou and Y. Chen, Ameliorative effects of functional crude-chalaza hydrolysates on the hepatosteatosis development induced by a high-fat diet, Poult. Sci., 2021, 100, 101009.
83. I. Fajriaty, I. Fidrianny, N. Kurniati, N. Fauzi, S. Mustafa and I. Adnyana, In vitro and in silico studies of the potential cytotoxic, antioxidant, and HMG CoA reductase inhibitory effects of chitin from Indonesia mangrove crab (Scylla serrata) shells, Saudi J. Biol. Sci., 2024, 31, 103964.
84. Z. Zhou, M. Wei, C. Tan, Z. Deng and J. Li, Low intake of ruminant trans fatty acids ameliorates the disordered lipid metabolism in C57BL/6J mice fed a high-fat diet, Food Funct., 2024, 15, 1539–1552.
85. K. Wang, Z. Fu, Y. Tan, H. Hong, J. Wu and Y. Luo, Silver carp muscle hydrolysate ameliorated atherosclerosis and liver injury in apoE-/- mice: the modulator effects on enterohepatic cholesterol metabolism, Food Sci. Hum. Wellness, 2024, 13, 3325–3338.
86. R. Tagawa, M. Kobayashi, M. Sakurai, M. Yoshida, H. Kaneko, Y. Mizunoe, Y. Nozaki, N. Okita, Y. Sudo and Y. Higami, Long-Term Dietary Taurine Lowers Plasma Levels of Cholesterol and Bile Acids, Int. J. Mol. Sci., 2022, 23, 1793.
87. S. Lee and B. Youn, Hypolipidemic Roles of Casein-Derived Peptides by Regulation of Trans-Intestinal Cholesterol Excretion and Bile Acid Synthesis, Nutrients, 2020, 12, 3058.
88. Q. Song, S. Kobayashi, Y. Kataoka and H. Oda, Direct Molecular Action of Taurine on Hepatic Gene Expression Associated with the Amelioration of Hypercholesterolemia in Rats, Antioxidants, 2024, 13, 990.
89. X. Zhang, F. Zhao, T. Ma, Y. Zheng, J. Cao, C. Li and K. X. Zhu, UPLC-Q-TOF/MS-based metabonomics reveals mechanisms for Holothuria leucospilota polysaccharides (HLP)-regulated serum metabolic changes in diabetic rats, Food Chem.:X, 2023, 19, 100741.
90. C. Kok, D. Rose and R. Hutkins, Predicting Personalized Responses to Dietary Fiber Interventions: Opportunities for Modulation of the Gut Microbiome to Improve Health, Annu. Rev. Food Sci. Technol., 2023, 14, 157–182.
91. S. Yao, Y. Zhong, Y. Cai, H. Chen, X. Xiang, Y. Zhou and L. Chen, Improvement mechanism of lipid metabolism and gut microbiota in obese mice with Thunnus albacares eggs yolk glycoprotein, J. Funct. Foods, 2024, 114, 106057.
92. Y. Liao, Q. Chen, L. Liu, H. Huang, J. Sun, X. Bai, C. Jin, H. Li, F. Sun, X. Xiao, Y. Zhang, J. Li, W. Han and S. Fu, Amino acid is a major carbon source for hepatic lipogenesis, Cell Metab., 2024, 36, 2437–2448.
93. T. Li, X. Chen, D. Huo, M. Arifuzzaman, S. Qiao, W. Jin, H. Shi, X. Li, I. Iliev, D. Artis, C. Guo and J. Consortium, Microbiota metabolism of intestinal amino acids impacts host nutrient homeostasis and physiology, Cell Host Microbe, 2024, 32, 661–675.
94. E. Brown, J. Clardy and R. Xavier, Gut microbiome lipid metabolism and its impact on host physiology, Cell Host Microbe, 2023, 31, 173–186.
95. C. Rai and P. Priyadarshini, Whey protein hydrolysates improve high-fat-diet-induced obesity by modulating the brain-peripheral axis of GLP-1 through inhibition of DPP-4 function in mice, Eur. J. Nutr., 2023, 62, 2489–2507.
96. R. Wang, X. Yang, Q. Jiang, L. Chen, S. Gu, G. Shen, S. Liu and X. Xiang, Effect of mussel polysaccharide on glucolipid metabolism and intestinal flora in type 2 diabetic mice, J. Sci. Food Agric., 2023, 103, 3353–3366.
97. J. Luo, M. Chen, H. Ji, J. Chen, W. Song, D. Zhang, W. Su, S. Liu and J. Majura, Regulates macrophage polarization via the lipophage-NLRP3 inflammasome to ameliorate atherosclerosis in ApoE^−/− mice, J. Funct. Foods, 2024, 118, 106280.
98. M. Zhao, D. Zhang, Q. Zhang, Y. Lin and H. Cao, Association between composite dietary antioxidant index and hyperlipidemia: a cross-sectional study from NHANES (2005-2020), Sci. Rep., 2024, 14, 15935.
99. M. Wu, Q. Xi, Y. Sheng, Y. Wang, W. Wang, C. Chi and B. Wang, Antioxidant Peptides from Monkfish Swim Bladders: Ameliorating NAFLD In Vitro by Suppressing Lipid Accumulation and Oxidative Stress via Regulating AMPK/Nrf2 Pathway, Mar. Drugs, 2023, 21, 360.
100. J. Ou, X. Liu, J. Chen, H. Huang, Z. Wang, B. Xu and S. Zhong, Amelioration of arsenic-induced hepatic injury via sulfated glycosaminoglycan from swim bladder: Modulation of Nrf2 pathway and amino acid metabolism, Int. J. Biol. Macromol., 2025, 287, 138528.
101. R. Hosomi, R. Otsuka, H. Arai, S. Kanda, T. Nishiyama, M. Yoshida and K. Fukunaga, Porcine hemoglobin promotes lipid excretion to feces more strongly than globin protein in rats, Food Sci. Biotechnol., 2016, 25, 107–112.
102. Z. DuAn, X. Ji, Y. Zhu, D. Zhao, K. Han, S. Gu, L. Ma, S. Jin, J. Chen, T. Li and N. Huo, Effects of Sheep Bone Collagen Peptide on Liver Lipid Deposition in Ovariectomized Rats, J. Nutr. Sci. Vitaminol., 2022, 68, 320–330.
103. P. Ghaffari-Bohlouli, H. Jafari, N. Taebnia, A. Abedi, A. Amirsadeghi, S. Niknezhad, H. Alimoradi, S. Jafarzadeh, M. Mirzaei, L. Nie, J. Zhang, R. Varma and A. Shavandi, Protein by-products: Composition, extraction, and biomedical applications, Crit. Rev. Food Sci. Nutr., 2023, 63, 9436–9481.
104. Y. Zhang, X. Bao, Y. Zhu, Z. Dai, Q. Shen and Y. Xue, Advances in machine learning screening of food bioactive compounds, Trends Food Sci. Technol., 2024, 150, 104578.
105. Y. Gu, L. Shuai, D. Li, M. Song, Y. Liu and X. Yang, Characterization of the daucosterol-lecithin complex and its impact on lipid metabolism in hyperlipidemic mice, RSC Adv., 2024, 14, 27354–27364.
106. Y. Niu, Q. Xia, W. Jung and L. Yu, Polysaccharides-protein interaction of psyllium and whey protein with their texture and bile acid binding activity, Int. J. Biol. Macromol., 2019, 126, 215–220.
107. L. Pang, R. Li, Z. Huang, X. Yang and Y. Jiang, Milk protein-polyphenol-saccharide ternary complexes: Improved health and functional properties, Curr. Opin. Food Sci., 2025, 61, 101239.
108. S. Kamchonemenukool, Y. Koh, P. Ho, M. Pan and M. Weerawatanakorn, Fatty Acid Esterification of Octacosanol Attenuates Triglyceride and Cholesterol Synthesis in Mice, J. Agric. Food Chem., 2025, 73, 2430–2442.
109. A. Santini and E. Novellino, Nutraceuticals in hypercholesterolaemia: an overview, Br. J. Pharmacol., 2017, 174, 1450–1463.
110. R. Cao, J. Li, Y. Sun, Y. Li, X. L. Zhang, H. Ding and X. Liu, Synthesis, characterization, and in vitro hypolipidemic mechanisms of sugar-SA triazole conjugates as potent pancreatic lipase inhibitors, Food Chem., 2025, 488, 144876.
111. T. Li, L. Liu, K. Zhu, Y. Luo, X. Huang, Y. Dong and J. Huang, Biomimetic MicroRNAs-Selenium-Nanocomposites for Targeted and Combined Hyperlipidemia Therapy, Adv. Healthcare Mater., 2024, 13, 2400064.
112. L. Zuo, Q. Liu, Y. Yu, Y. Fan, L. Zhu, C. Xu, B. Wei, J. Zhang and H. B. Wang, Collagen peptide decorated selenium nanoparticles: preparation, characterization, hypolipidemic, and antitumor activities, Part. Sci. Technol., 2025, 43, 178–187.
113. M. Yi, Y. Zhang, L. Zhang, Y. Li, H. Zhang, Q. Z. Jin, G. Wu and X. Wang, Screening of fish oil fatty acids for antihyperlipidemic activity based on network pharmacology and validation of synergistic efficacy in vitro, Food Biosci., 2024, 58, 103745.
114. A. Wu, F. Yang, H. Zhong, J. Hong, H. Lin, M. Zong, H. Ren, S. Zhao, Y. Chen, Z. Shi, X. Wang, J. Shen, Q. Wang, M. Ni, B. Chen, Z. Cai, M. Zhang, Z. Cao, K. Wu, A. Gao, J. Li, C. Liu, M. Xiao, Y. Li, J. Shi, Y. Zhang, X. Xu, W. Gu, Y. Bi, G. Ning, W. Wang, J. Wang and R. Liu, Obesity-enriched gut microbe degrades myo -inositol and promotes lipid absorption, Cell Host Microbe, 2024, 32, 1301–1314.
115. L. Derosa, V. Iebba, C. Silva, G. Piccinno, G. Wu, L. Lordello, B. Routy, N. Zhao, C. Thelemaque, R. Birebent, F. Marmorino, M. Fidelle, M. Messaoudene, A. Thomas, G. Zalcman, S. Friard, J. Mazieres, C. Audigier-Valette, D. Moro-Sibilot, F. Goldwasser, A. Scherpereel, H. Pegliasco, F. Ghiringhelli, N. Bouchard, C. Sow, I. Darik, S. Zoppi, P. Ly, A. Reni, R. Daillère, E. Deutsch, K. Lee, L. Bolte, J. Björk, R. Weersma, F. Barlesi, L. Padilha, A. Finzel, M. Isaksen, B. Escudier, L. Albiges, D. Planchard, F. André, C. Cremolini, S. Martinez, B. Besse, L. Zhao, N. Segata, J. Wojcik, G. Kroemer and L. Zitvogel, Custom scoring based on ecological topology of gut microbiota associated with cancer immunotherapy outcome, Cell, 2024, 187, 3373–3389.
116. W. Wei, C. Wong, Z. Jia, W. Liu, C. Liu, F. Ji, Y. Pan, F. Wang, G. Wang, L. Zhao, E. Chu, X. Zhang, J. Sung and J. Yu, Parabacteroides distasonis uses dietary inulin to suppress NASH via its metabolite pentadecanoic acid, Nat. Microbiol., 2023, 8, 1534–1548.
117. Y. Fan, M. Qin, J. Zhu, X. Chen, J. Luo, T. Chen, J. Sun, Y. Zhang and Q. Xi, MicroRNA sensing and regulating microbiota-host crosstalk via diet motivation, Crit. Rev. Food Sci. Nutr., 2024, 64, 4116–4133.
118. V. Rioux-Labrecque, M. Cossette, M. Ru, D. Bilodeau, M. C. Guertin and J. Tardif, Supplementation with a β-glucan tablet has no effect on hyperlipidemia: a randomized, placebo-controlled clinical trial, Am. J. Clin. Nutr., 2023, 117, 1232–1239.
119. G. Ren, L. He, Y. Liu, Y. Fei, X. Liu, Q. Lu, X. Chen, Z. Song and J. Wang, The long-term intake of milk fat does not significantly increase the blood lipid burden in normal and high-fat diet-fed mice, iMeta, 2024, 3, e256.
120. N. Quinn-Bohmann, T. Wilmanski, K. Sarmiento, L. Levy, J. Lampe, T. Gurry, N. Rappaport, E. Ostrem, O. Venturelli, C. Diener and S. Gibbons, Microbial community-scale metabolic modelling predicts personalized short-chain fatty acid production profiles in the human gut, Nat. Microbiol., 2024, 9, 1700–1712.
121. Z. Wang, L. Wang, Y. Hou, X. Zhang, H. Wang, S. Zhang, C. Du and J. Huang, Precision calories: A promising strategy for personalized health interventions in the precision nutrition framework, Trends Food Sci. Technol., 2024, 153, 104727.
122. G. Carrera-Alvarado, F. Toldrá and L. Mora, Bile acid-binding capacity of peptide extracts obtained from chicken blood hydrolysates using HPLC, LWT – Food Sci. Technol., 2023, 173, 1143.

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