Extracellular vesicles in obesity: linking postprandial metabolism to metabolic dysfunction

Abstract

Obesity is a major global health burden closely linked to cardiovascular complications, particularly cardiovascular disease (CVD). Extracellular vesicles (EVs), membrane-bound particles released by most cell types, mediate intercellular communication by transporting bioactive lipids, proteins, and nucleic acids. In obesity and related metabolic disorders, shifts in EV abundance, cellular origin, and cargoes have been associated with endothelial dysfunction, insulin resistance, and thrombo-inflammation. This narrative review critically appraises how postprandial metabolism reshapes the EV profile and functionality, integrating recent omics-based and mechanistic studies while distinguishing association from causality. We also examine diet–EV interactions, including how the quantity and quality of dietary fat may reprogramme EV lipids and miRNA cargoes. Evidence for food-derived EVs is emerging, but currently supports only partial gastrointestinal resistance and context-dependent bioactivity. Throughout, we highlight key methodological constraints and emphasize pre-analytical adherence to MISEV guidelines to improve reproducibility and translational relevance. Collectively, clarifying EV dynamics in the postprandial state may advance their use as clinically meaningful biomarkers and potential targets for mitigating obesity-related metabolic dysfunction through informed dietary and lifestyle interventions.

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Metabolic dysregulation in obesity: an overview

Obesity is a major health burden strongly associated with systemic complications, particularly cardiovascular disease (CVD).¹ Its multifactorial nature has driven diverse investigative approaches to disentangle molecular and physiological mechanisms underlying metabolic dysfunction. Among the most active areas, extracellular vesicles (EVs) have emerged as the key mediators of intercellular communication. Although EV classification remains operational, typically based on biogenesis, size, cellular origin, and molecular cargoes, the field commonly refers to small EVs (often enriched for exosome markers) and microvesicles. Regardless of the nomenclature, EVs are released by virtually all cell types and can carry bioactive lipids, proteins, and nucleic acids that influence distant tissues, thereby potentially contributing to obesity-related pathologies.²

The postprandial period offers a dynamic stress test of metabolic homeostasis. After a meal, coordinated changes in lipoprotein fluxes, endocrine signals, and inflammatory tone expose latent vulnerabilities in cardiometabolic control. Emerging evidence shows that EV profiles are highly plastic postprandially, with shifts in abundance, cellular origin, and cargoes.^3,4 These changes have been linked to endothelial activation/dysfunction, platelet–leukocyte crosstalk, and innate immune pathways, underscoring EVs as both reported and potential effectors at the intersection of metabolism and inflammation.

Mechanistically, nutrient load and lipoprotein handling (e.g., chylomicrons and their remnants), lipolysis products, oxidative stress, and transient endotoxemia can modulate EV release and composition across endothelial, platelet, leukocyte, adipose, hepatic, and intestinal compartments. Alterations in EV surface markers and molecular cargoes (lipid species, miRNAs and proteins) may, in turn, affect insulin signalling, vascular reactivity, and thrombo-inflammatory pathways, providing plausible links between dietary exposure, postprandial responses, and longer-term metabolic risk.

Diet and lifestyle appear to modulate EV dynamics.⁵ Human and mechanistic studies indicate that the quantity and quality of fat, overall dietary patterns, and physical activity can influence EV abundance, cellular origin, and cargoes. Evidence for food-derived EVs (FDVs) is intriguing but still preliminary; current data support partial gastrointestinal resistance and context-dependent bioactivity rather than universal systemic uptake. Accordingly, this review summarizes current knowledge on EV dynamics in the postprandial state, their involvement in obesity and related disorders, and the influence of modifiable factors, while emphasizing methodological constraints and the need for standardized workflows to strengthen causal inference and translational relevance. We conducted a structured literature search (January 2005–January 2025) in PubMed/MEDLINE and Web of Science using combinations of: ‘extracellular vesicles’ OR ‘exosomes’ OR ‘microvesicles’ AND ‘postprandial’ OR ‘meal’ OR ‘dietary fat’ OR ‘lipemia/lipaemia’ AND ‘obesity’ OR ‘insulin resistance’ OR ‘endotheli’ OR ‘thrombo*’. We prioritized original human studies and mechanistic animal/cell models evaluating EV abundance, cellular origin, or cargoes in postprandial contexts or obesity, and included relevant reviews/guidelines (e.g., MISEV). Exclusion criteria were non-English studies; nanoparticles not of biological origin; studies lacking EV characterization beyond size or a single marker; and preprints without peer review. Reference lists of eligible articles were screened for additional records. As this is a narrative review, no formal risk-of-bias or meta-analysis was performed.

Extracellular vesicles: biogenesis, cargoes, and functional relevance

EVs are membrane-enclosed carriers of diverse biomolecules that have garnered increasing attention since the discovery that they are not merely cellular waste, but active mediators of intercellular communication and tissue homeostasis.⁶ EV nomenclature and classification remain operational: although terms based on size (e.g., small vs. large EVs) or context (oncosomes and migrasomes) are used; the most common distinction refers to their biogenesis, separating small EVs of endosomal origin (often enriched for exosome markers) from microvesicles (plasma-membrane budding) and apoptotic bodies (cell death-related vesicles).⁷ In practice, strict discrimination is challenging due to overlapping size ranges and marker repertories, as well as isolation-dependent biases.

Endosomal (exosome-enriched) EVs, typically ∼30–150 nm, arise from inward budding of the endosomal membrane to form intraluminal vesicles within multivesicular bodies (MVBs) (Fig. 1). MVBs either fuse with lysosomes for cargo degradation or with the plasma membrane to release their intraluminal vesicles as EVs. The endosomal sorting complex required for transport (ESCRT) machinery coordinates cargo selection and membrane budding (ESCRT-0/I/II) and membrane scission (ESCRT-III), although ESCRT-independent routes have also been described, underscoring context-dependent regulation of EV biogenesis.⁸ In contrast, microvesicles (∼50–1000 nm) bud outward directly from the plasma membrane through phospholipid distribution and cytoskeletal remodelling (actin–myosin), while apoptotic bodies originate during programmed cell death and often contain cytoplasmic and nuclear fragments.⁹

Fig. 1 Schematic representation of the biogenesis, release, and molecular composition of extracellular vesicles (EVs). EVs originate from the endosomal system through the formation of multivesicular bodies (MVBs) or via direct budding from the plasma membrane. The process involves endocytosis, trafficking through early and late sorting endosomes, and fusion of MVBs with the plasma membrane, leading to exocytosis and EV release. The molecular composition of EVs includes proteins (e.g., β-catenin, TGF-β, HIF1α and caveolin-1), lipids (e.g., phospholipids, galactolipids, cholesterol and ceramides), nucleic acids (miRNAs, mRNAs and DNAs), heat shock proteins (HSP60, HSP70 and HSP90), and metabolites (e.g., glycerol, naringenin, vitamin C and sulforaphane). Transmembrane proteins (e.g., CD9, CD63 and CD81) are key markers of EVs.

The biological significance of EVs stems from their rich and selectable cargoes, proteins, lipids, mRNAs, miRNAs, and metabolites, and their ability to engage recipient cells via surface ligands/receptors, membrane fusion, and endocytosis. This enables EVs to act as both local and systemic messengers that mirror the cellular state and can modulate phenotypes in target tissues. Omics profiling (proteomics, lipidomics and transcriptomics) across EVs from multiple tissues has revealed disease-associated signatures, but also substantial methodological heterogeneity that complicates cross-study comparisons.

Protein signatures frequently reported in small EVs include tetraspanins (CD9/CD63/CD81), ESCRT-associated proteins (e.g., ALIX and TSG101), scaffold/adaptor proteins, small GTPases, and other membrane/peripheral proteins (WNT).¹⁰ Such markers have supported immunoaffinity approaches and candidate biomarker discovery, though their universality varies with cellular origin and stress context, arguing for multi-marker panels rather than single universal markers. Examples of applications to human disease include putative urinary EV protein markers for prostate cancer,¹¹ EV-associated proteins linked to autoimmune pathophysiology¹² and pathogen-derived proteins detected within EVs in neuroinflammatory settings.¹³

EV lipid composition is a functional determinant rather than a passive membrane scaffold. EV membranes are typically enriched in sphingolipids (e.g., ceramides and sphingomyelins), cholesterol, phosphatidylethanolamines, diacylglycerols, and lysobisphosphatidic acid.¹⁴ Disease-related remodelling of EV lipids has been reported, for instance, EVs associated with amyloid pathology showing enrichment in gangliosides/ceramides¹⁵ and EV lipid changes linked to airway inflammation in asthma,¹⁶ although most evidence remains correlative and sensitive to analytical workflows.

miRNAs constitute another key cargo layer. Selective sorting yields EV miRNA profiles that diverge from their parent cells, supporting regulated packaging and targeted delivery to recipient cells, where they can modulate gene expression programmes involved in differentiation, proliferation, or migration.¹⁷ Disease-focused studies have associated EV miRNAs with tumour progression via repression of tumour suppressors¹⁸ and with neurodegenerative processes and neuroinflammation.¹⁹ As with proteins and lipids, robust interpretation benefits from integrating EV miRNAs with cellular origin markers, appropriate negative controls for contaminants, and harmonized reporting.

In summary, EVs act as both mirrors (biomarkers of cellular state) and mediators (functional effectors) of physiology and disease. Their molecular heterogeneity is biologically informative but methodologically demanding; rigorous attention to pre-analytical handling, isolation/quantification strategies, and marker panels is essential to ensure reproducibility and to translate EV insights to metabolic, neurological, oncological, and, as explored in this review, obesity-related and postprandial contexts.

Extracellular vesicles in postprandial metabolism

Postprandial lipaemia denotes the transient rise in circulating triacylglycerol (TAG) following meal ingestion, largely driven by TAG-rich lipoproteins (TRLs). Although TRLs are predominantly chylomicrons of intestinal origin, VLDLs of hepatic origin often contribute. The magnitude and duration of postprandial lipaemia depend on intestinal fat absorption, chylomicron secretion, intravascular clearance of TRLs, and VLDL metabolism/turnover.²⁰ This physiological process becomes pathological when TAG elevations are excessive and prolonged, a state linked to higher cardiometabolic risk. The type and amount of dietary fat, together with determinants of TRL synthesis, clearance, and re-uptake, shape the plasma lipoprotein balance.²¹

Beyond lipid excursions, the postprandial state is a period of intense metabolic–immune crosstalk. Coordinated shifts in lipoprotein fluxes, endocrine signals, and inflammatory tone can unmask vulnerabilities in cardiometabolic control. It is well established that postprandial lipaemia can induce low-grade inflammation via TLR/complement (C3) activation, leukocyte activation and neutrophilia, cytokine production, and oxidative stress.²² Diets rich in saturated fatty acids (SFAs) exacerbate these responses by increasing IL-6 and TNF-α, whereas monounsaturated fatty acids (MUFAs, e.g., oleic acid from olive oil)²³ and omega-3 long-chain polyunsaturated fatty acids (ω3-LCPUFAs)²⁴ attenuated chronic low-grade inflammation. Frequent bouts of postprandial hypertriglyceridemia contribute to the pro-inflammatory phenotype of obesity and increase CVD risk.²⁵

Within this context, EVs are emerging as reporters and potential effectors of the postprandial response, although their contribution remains incompletely defined. Recent studies show postprandial shifts in EV abundance, cellular origin, and cargoes, but results for particle counts and size distributions are heterogeneous and often constrained by methodology.^5,26,27 Contributing factors include: (i) differing sampling windows (e.g., 2–8 h), (ii) co-isolation with lipoproteins due to overlapping size/density, (iii) variable isolation strategies (ultracentrifugation, SEC and immunocapture), (iv) quantification platforms (NTA, flow cytometry and TRPS) with different sensitivities, and (v) normalization choices (volume, protein and cell counts). Harmonized workflows and MISEV-aligned reporting are essential to separate biological variations from technical artefacts.

Functionally, several routes connect EVs with postprandial homeostasis. EV may expose phosphatidylserine and tissue factor, determinants of procoagulant activity, linking vesicle dynamics to endothelial activation and thrombosis risk.²⁸ This axis remains understudied but is particularly relevant in chronically high-fat dietary patterns. Regarding lipid trafficking, Garcia et al.²⁹ reported postprandial enrichment of EVs in lipids and the CD36 fatty acid transporter, facilitating long-chain fatty acid uptake by recipient cells. These data support a role for EVs in lipid transfer from circulation to peripheral tissue; however, a key challenge is distinguishing EV-mediated transport from lipoprotein-mediated exchange, which co-occur in plasma.

At the post-transcriptional level, Mantilla-Escalante et al.³⁰ observed postprandial changes in circulating EV miRNAs, including increases in miR-206, miR-409-3p, and miR-27b-5p. The latter has been implicated in metabolic dysfunction through modulation of PPARy and hepatic lipid metabolism.³¹ While suggestive, the causal relevance of these miRNA fluctuations remains to be established and warrants mechanistic studies linking EV cargoes to metabolic endpoints in humans. Consistent with the modifiability of EV miRNAs in dietary contexts, an acute randomized crossover trial reported that a cocoa–carob blend altered exosomal miRNAs related to insulin sensitivity in type 2 diabetes, despite limited acute effects on classical glycemic/GLP-1 endpoints—highlighting EV miRNAs as sensitive readouts and the need for long-term interventions to test causality.³²

More recently, Garza et al.³³ profiled the proteome and cellular origin of EVs in pre- vs. postprandial states. Although total EV concentrations and protein content were relatively stable, CD324⁺-EVs (an epithelial intestinal marker) increased postprandially, suggesting active intestinal release in response to nutrient exposure and a potential role in gut–liver/vascular signalling. This supports the emerging view of the intestine as an endocrine organ and positions EVs as novel mediators of metabolic communication.

Collectively, current evidence supports EVs as integral components of the physiological response to nutrient intake, yet their precise contribution to postprandial homeostasis is not fully defined. Since disorders such as obesity resemble a state of sustained hyperlipidaemia, defining the phenotypic and functional properties of EVs in healthy and obese individuals should clarify mechanisms of metabolic dysregulation. Such knowledge may guide nutritional strategies to mitigate inflammatory and metabolic complications of obesity and CVD.

Extracellular vesicles in the pathophysiology of obesity

The global burden of obesity has risen sharply in recent years and continues to increase, particularly in high-income settings. According to the World Health Organisation (WHO),³⁴ more than one billion people worldwide were classified as obese in 2022, approximately one in eight individuals. Obesity develops when energy intake chronically exceeds expenditure, leading to excess TAG storage in adipose depots and ectopic sites. In obese individuals, lipid accumulation is accompanied by chronic low-grade inflammation, a key driver of metabolic complications including hypertension, dyslipidaemia, diabetes, CVD, and some cancers. Among the most affected organs is adipose tissue. Mammals possess white adipose tissue (WAT), primarily an energy reservoir that stores lipids and releases fatty acids for oxidation, and brown adipose tissue (BAT), which contributes to non-shivering thermogenesis and energy expenditure. Together they support metabolic homeostasis through endocrine and paracrine outputs, including hormones (e.g., leptin and adiponectin), growth factors (e.g., IGF-1 and VEGF), cytokines (e.g., TNF-α and IL-6), and enzymes.³⁵ During caloric restriction, higher adiponectin is associated with improved metabolic and cardiovascular profiles. In obesity, however, the adipose tissue microenvironment is remodelled, and immune infiltration, hypoxia, and extracellular matrix changes alter secretory programmes and inter-organ crosstalk.³⁶ Within this disrupted dialogue, EVs have emerged as key mediators shuttling bioactive molecules between adipose depots and peripheral tissues.

A growing body of evidence implicates EVs in metabolic balance and its dysregulation in obesity (Fig. 2). Adipose tissue is a major EV source, and depot-specific differences in EV abundance and cargoes suggest that visceral and subcutaneous fat communicate differently with systemic targets. In obesity, circulating EVs enriched for pro-inflammatory factors, including IL-6, macrophage secretion inhibitory factor (MIF), and MCP-1, have been reported. MIF, for example, can promote macrophage M1 polarization via ERK signalling, increasing secretion of IL-1β, interferons, and chemokines.^37,38 Notably, assigning these signals to a single tissue of origin is challenging because circulating EVs are heterogeneous; rigorous attribution requires appropriate isolation, origin markers, and controls.

Fig. 2 Adipose tissue-derived extracellular vesicle (EV) cargoes and their alteration in the course of obesity. Under healthy conditions, EVs derived from white adipocytes contribute to adipose tissue homeostasis by regulating insulin sensitivity, adipogenesis, and anti-inflammatory signaling. These EVs transport bioactive molecules, including miRNAs (e.g., miR-155, miR-27a and miR-130b), proteins (e.g., adiponectin and MIF), and lipids, which support immune homeostasis, improve glucose tolerance, enhance insulin sensitivity, and promote lipid oxidation. In obesity, hypertrophied white adipocytes release EVs enriched in pro-inflammatory miRNAs (e.g., miR-34, miR-33, miR-145 and miR-1224), proteins (e.g., FABP4, IL-6 and MCP-1), and other factors that drive macrophage recruitment and polarization towards the pro-inflammatory M1 phenotype. These alterations promote chronic inflammation, insulin resistance, and metabolic dysfunction, leading to systemic insulin resistance, increased lipid accumulation, and decreased lipid oxidation.

Among EV-associated proteins linked to adipose biology, perilipin 1 (PLIN1), a lipid droplet scaffold from the PAT family, regulates storage and lipolysis in adipocytes.³⁹ Under basal conditions, PLIN1 restrains ATGL and HSL activities, limiting lipolysis and downstream eicosanoid synthesis, thereby dampening macrophage recruitment and NF-κB-dependent cytokine production. In obesity, PLIN1-positive EVs are increased in circulation while adipocyte PLIN1 is reduced, a pattern associated with monocyte infiltration, cytokine release, adipose inflammation, and insulin resistance.⁴⁰ These observations support PLIN1-EVs as potential markers of adipose dysfunction; whether they act as passive indicators or active amplifiers remains to be clarified in mechanistic models. Other EV proteins, such as MMP-2, transforming growth factor beta-inducible (βig-h3), thrombospondin-1, FABP4, mimecan, and ceruloplasmin, have been reported. While FABP4 has been proposed as a marker of obesity and insulin resistance, the downstream consequences of elevated EV-associated FABP4 are not fully defined, leaving open whether these vesicles drive remodeling or primarily mirror intracellular stress.⁴¹

Among EV cargoes, miRNAs have attracted considerable interest because of their pleiotropic, rapid regulatory effects on adipose biology. Ferrante et al.⁴² identified 55 differentially expressed miRNAs in exosomes from visceral adipose tissues of obese versus healthy controls, including downregulated miR-148b and miR-4269 and upregulated miR-23b and miR-4429, which map to TGF-β and Wnt/β-catenin pathways influencing growth, differentiation, and immune responses. Although compelling, these associations remain correlative; causal contribution to systemic insulin resistance or adipose inflammation requires functional validation.

Further insights come from work showing that adipocyte-derived EVs from obese individuals overexpress miR-34, which inhibits polarization toward the anti-inflammatory M2 phenotype, thereby sustaining inflammation and metabolic dysregulation.⁴³ Likewise, miR-1224 in adipocyte-derived exosomes targets MSI2 and inhibits Wnt/β-catenin, impairing M2 polarization.⁴⁴ Conversely, miR-690 levels in M2 macrophage-derived exosomes are reduced in obesity, contributing to impaired NAD⁺ biosynthesis and insulin resistance.⁴⁵ Together, these studies support bidirectional EV-mediated communication between adipocytes and immune cells; however, the temporal sequence, depot specificity, and in vivo effect sizes remain to be defined.

Beyond adipose-derived vesicles, endothelial- and platelet-derived EVs are altered in obesity and may contribute to cardiovascular risk. Elevated endothelial EVs enriched in adhesion molecules (VCAM-1 and ICAM-1) are reported in individuals with impaired glucose metabolism, consistent with vascular inflammation.⁴⁶ Platelet-EVs, increased in obesity, carry cytokines (e.g., IL-1β, TNF-α and CCL-2), adhesion molecules (e.g., ICAM-1), lipid mediators, and damage-associated molecular patterns, thereby amplifying inflammation, leukocyte recruitment, and thrombogenesis.^47,48 These vesicles also transport miR-155, a pro-inflammatory regulator implicated in adipose–muscle and vascular crosstalk.⁴⁹

Macrophage-derived EVs further shape metabolic homeostasis. Adipocyte EVs promote macrophage accrual and M1 polarization within adipose tissue, while macrophage-EVs signal to distant organs. Ying et al.⁵⁰ showed that obesity-associated pro-inflammatory exosomes enriched in miR-155 suppress PPARγ signalling, impair B-cell function, reduce insulin secretion, and promote diabetes development (Table 1). Systemic characterization of macrophage-derived EV content and function in adipose tissue remains a priority.⁵¹

Table 1 Evidence for the contribution of the molecular content of EVs in the pathophysiology of obesity

EV component	EV origin	Source of EVs	Function in obesity	Ref.
IL-6, MIF and MCP-1	Circulating exosomes	Human plasma	Promote M1 macrophage polarization via ERK activation and inhibit neutrophil apoptosis, exacerbating inflammation	37 and 38
PLIN1	Adipocyte-derived exosomes	Animals (diet-induced obese mice)	Elevated in circulation; associated with altered lipid metabolism, increased adipose tissue inflammation, and insulin resistance	40
MMP-2, βig-h3, thrombospondin-1, FABP4, mimecan, ceruloplasmin, TGFBI, CD14, CAVN1 and AHNAK	Visceral adipose tissue-derived exosomes	Humans (adipose tissue from obese subjects)	Enriched in VAT-EVs from obese individuals; associated with adipose tissue inflammation, insulin resistance, and metabolic dysfunction. TGFBI-EVs were linked to T2D progression, while mimecan-EVs correlated with visceral adiposity	41
miR-148b, miR-4269, miR-23b and miR-4429	Visceral adipose tissue-derived exosomes	Humans (obese patients)	Dysregulated in obesity; modulate TGF-β and Wnt/β-catenin signaling, impacting adipogenesis, inflammation, and metabolic homeostasis	42
miR-34a	Adipocyte-derived exosomes	Animals (diet-induced obese mice)	Inhibits M2 macrophage polarization by targeting Krüppel-like factor 4 (KLF4), leading to sustained adipose tissue inflammation and metabolic dysfunction	43
miR-1224	Adipocyte-derived exosomes	Animals (HFD-induced obese mice)	Inhibits M2 macrophage polarization via MSI2-mediated Wnt/β-catenin signaling, promoting obesity-induced adipose tissue inflammation	44
miR-690	M2 macrophage-derived exosomes	Animals (HFD and ApoE−/− mice)	Reduces exosomal levels of miR-690, impairing NAD+ biosynthesis and contributing to insulin resistance in obesity	45
Microparticles enriched in VCAM-1 and ICAM-1	Endothelial-derived EVs	Humans (plasma, prediabetic and T2D subjects)	Elevated in obesity; these EVs are associated with endothelial inflammation and vascular dysfunction, contributing to increased cardiovascular risk in obese individuals	46
IL-1β, TNF-α, CCL-2, ICAM-1 and lipid mediators	Platelet-derived and endothelial-derived EVs	In vitro (human endothelial cells stimulated with TNF-α)	Transport inflammatory cytokines and lipid mediators, promoting thrombosis and leukocyte recruitment, and amplifying the inflammatory environment, contributing to obesity-related cardiovascular complications	47 and 48
miR-155	Visceral adipocyte-derived exosomes	Animals (HFD-induced obese mice; adipose–muscle co-culture and AAV model)	Impairs skeletal muscle homeostasis by inhibiting myogenesis directly through exosomal miR-155 transfer and indirectly via macrophage-mediated inflammation	49

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In sum, EVs are not merely bystanders but active participants in the disrupted communication networks of obesity. Their ability to transfer lipids, proteins, and genetic material across tissues places them at the interface of metabolic and immune regulation. However, progress is currently limited by heterogeneous study designs, small cohorts, and variable isolation/characterization methods. Future work should integrate standardized EV workflows with multi-omics and clinically anchored endpoints to determine whether EV modulation is predominantly a consequence or a driver of obesity, and whether nutritional interventions or specific dietary components can meaningfully recalibrate EV-mediated signaling to reverse metabolic disease.

Dietary modulation of extracellular vesicles and the role of food-derived vesicles

Given the positioning of EVs at the crossroads of metabolism and inflammation, diet emerges as a plausible lever to modulate EV abundance, cellular origin, and cargoes. Conceptually, EV-associated molecules linked to obesity (e.g., specific lipids, proteins and miRNAs) could serve as biomarkers of dietary exposure and metabolic status, and, in the longer term, as modifiable targets for nutrition-based strategies. However, direct evidence in humans remains limited, and findings are often constrained by heterogeneous protocols and small samples. Rigorous, MISEV-aligned designs are needed before EVs can be incorporated into routine nutritional phenotyping.

Dietary patterns as modulators of EV profiles

Lifestyle interventions reveal the plasticity of EVs, although most studies emphasize phenotypic counts/markers rather than molecular cargoes. High-fat diets have long been linked to increased circulating EVs: for example, Heinrich et al.⁵² reported higher plasma EVs in obese rats fed a high-fat diet, alongside enhanced endothelial VCAM-1 expression induced by these vesicles, consistent with a more pro-atherogenic milieu. In humans, recent evidence suggests that weight loss, achieved via diet, combined diet-plus-exercise, or bariatric surgery, can reduce circulating leukocyte- and platelet-derived EVs – vesicle classes implicated in thrombosis and elevated cardiovascular risk.^53,54 Thrush et al.⁵⁵ showed that plasma exosomes from weight-loss responders (vs. weight-loss resistant individuals) enhanced fatty acid metabolism and increased resting, drug stimulation, and maximal oxygen consumption in cultured myotubes. These observations indicate that metabolic benefits after dietary intervention likely involve qualitative remodeling of intercellular communication via EVs, not merely weight reduction per se.

The impact of diet on EV cargoes is less well understood but is emerging. Both the amount and composition of dietary lipids appear to shape EV content and, potentially, function. For instance, perilipin A levels increase in plasma EVs from mice on high-fat diets.⁵⁶ Palmitate-rich diets can promote exosome release from muscle cells with higher lipid content, potentially mediating palmitate's adverse effects on neighbouring tissues and contributing to insulin resistance and type 2 diabetes.⁵⁷ In adipocytes, exposure to oleate vs. palmitate alters the protein cargoes of adipose-derived EVs, reinforcing the idea that dietary lipids reprogramme EV composition and signalling.⁵⁸ Whether such lipid-driven cargo shifts are adaptive responses or early markers of lipotoxicity remains unresolved and will be critical for interpreting EVs as biomarkers of lipid quality.

Building on these findings, Kumar et al.⁵⁹ observed that intestinal epithelial-derived exosomes undergo phospholipid remodelling (phosphatidylethanolamine/phosphatidylcholine balance), promoting insulin resistance through AhR activation in hepatocytes, in high-fat diet-fed mice. Lysophosphatidylcholine increases in plasma with high-fat diets, and Hirsova et al.⁶⁰ found that lysophosphatidylcholine-treated hepatocytes released larger EVs enriched in integrin β1, fostering inflammation. Given lysophosphatidylcholine's role in macrophage recruitment,⁶¹ dietary patterns that elevate lysophosphatidylcholine may contribute to chronic low-grade inflammation via hepatocyte EV remodelling, suggesting that lowering lysophosphatidylcholine could be a nutritional avenue to attenuate EV-mediated inflammation. High-fat diets are also linked to MAFLD. Yan et al.⁶² reported that such diets increase plasma exosomes enriched in CD36, associated with hepatic lipid accumulation and inflammation. Cholesterol loading likewise alters EV profiles: Huh7 hepatocytes exposed to oxLDL release exosomes enriched in miR-122-5p, which promote macrophage M1 polarization.⁶³ Collectively, these mechanistic studies support vesicle-mediated lipid trafficking as a pathogenic link between dietary fat excess, hepatic steatosis, and systemic inflammation.

Beyond lipid cargoes, nutrition influences EV miRNA profiles. Parrizas et al.⁶⁴ observed that a hypocaloric diet reduced miR-192 and miR-193 in obese individuals, miRNAs previously associated with liver dysfunction⁶⁵ and immune dysregulation,⁶⁶ respectively, suggesting alignment between EV miRNA shifts and improved tissue function. Manning et al.⁶⁷ reported dysregulated EV miRNAs in obese women (implicated in cardiometabolic processes, cardiomyocyte survival, and β-cell maintenance), with normalization after weight loss. Furthermore, Mantilla-Escalante's group⁶⁸ found that one-year adherence to a Mediterranean diet rich in olive oil and nuts reduced miR-107 (linked to hepatic lipid accumulation/FLD), while miR-22-3p, a proposed therapeutic target for obesity/insulin resistance, also decreased.⁶⁹ These clinical observations support the modifiability of EV miRNAs with realistic dietary patterns, though stability, tissue specificity, and functional causality remain open questions.

Food-derived extracellular vesicles and their therapeutic potential

While the preceding sections focused on how diet and lifestyle modulate endogenous EVs, growing interest now centers on FDVs as putative bioactive components. Diverse plant- and animal-derived foods contain vesicle-like particles that can influence cellular processes in experimental systems. Although early interpretations were uncertain, current evidence indicates and supports partial gastrointestinal resistance of only a minority fraction of FDVs; survival and uptake appear highly context-dependent (source, isolation protocol, structural features, and food matrix).⁷⁰ The vesicular phospholipid bilayer may confer limited protection, enabling some particles to be internalized by intestinal epithelial cells and to act locally in the gut; systemic actions have been reported in preclinical models but remain incompletely established in humans. Across studies, findings depend strongly on EV origin and methodology, underscoring the need for standardized isolation/characterization and label-based tracer approaches before inferring bioavailability or tissue delivery.

FDVs from blueberries and citrus (e.g., lemon) have been reported to contain vitamin C and specific miRNAs that mitigate oxidative stress, reducing reactive oxygen species and improving cell viability in in vitro/animal models,⁷¹ with potential relevance to obesity-related complications such as diabetes.⁷² Aloe vera peel-derived vesicles have shown antioxidant activity linked to Nrf2 pathway activation.⁷³ Consistent with this, Zhao et al.⁷⁴ found that blueberry-derived vesicles attenuated oxidative stress, promoted nuclear translocation of Nrf2, and improved insulin resistance and liver dysfunction in a high-fat diet model, an important step toward causal mechanisms connecting dietary vesicle intake to metabolic outcomes. Translation to humans, however, remains to be demonstrated. Several plant FDVs exhibited immunomodulatory properties. Ginger-derived vesicles can deliver cargoes to macrophages, suppressing NLRP3 inflammasome activation¹³ and increasing anti-inflammatory mediators such as HO-1 and IL-10.⁷⁵ Similar effects have been described for FDVs from grapefruit⁷⁶ and garlic.¹³ Together, these observations support the concept that FDVs may tune host immune tone and redox balance, although the specific causal molecules (lipids, proteins and small RNAs) and their in vivo exposure–response relationships require clarification.

Among animal-derived foods, milk is the most extensively studied due to its abundance of vesicles. Omics profiling of milk-derived exosomes has identified miRNAs associated with diabetic complications,⁷⁷ motivating investigation into their role in human metabolic alterations and obesity. Owing to putative stability and bioavailability, milk-derived exosomes are being explored as natural drug-delivery carriers for metabolic indications. Recent work shows efficient encapsulation and transport of bioactives, reinforcing their potential as nanocarriers for therapeutic and functional applications.⁷⁸ These findings highlight the dual significance of FDVs, as intrinsic dietary bioactives and as innovative delivery vehicles in nutritional pharmacology. In summary, FDVs are increasingly recognized as bioactive dietary components with therapeutic potential, but clinical translation will require standardization, rigorous validation, and a deeper mechanistic understanding of exposure, bioavailability, and target engagement in humans.

Concluding remarks and future perspectives

This review highlights the intricate links between EVs, obesity, and metabolic disorders, with a specific focus on the postprandial state and dietary influence. EVs are not passive carriers but active mediators of intercellular communication that intersect metabolic and immune regulation. By shaping pathways related to inflammation, lipid handling, and insulin action, EVs are emerging as both biomarkers and candidate targets for metabolic risk modification.

The postprandial period provides a sensitive stress test of cardiometabolic control. Meal composition, especially the amount and quality of dietary fat, can remodel EV abundance, cellular origin, and cargoes, with implications for endothelial activation, thrombo-inflammation, and tissue fuel partitioning. In parallel, FDVs constitute a promising but still nascent area: current evidence supports partial, context-dependent gastrointestinal resistance of a minority fraction, with plausible local gut effects and only provisional support for systemic actions in humans.

Future research should prioritize several key areas. First, mechanistic resolution of inter-organ EV signalling in obesity. Deploy causal frameworks (randomized dietary interventions and mediation/perturbation analyses) that link defined EV changes to clinically anchored endpoints (insulin sensitivity, vascular function and thrombotic markers). Second, reduce technical variability via MISEV-aligned pre-analytical handling, harmonized sampling windows in postprandial studies, and transparent reporting of isolation/quantification methods (e.g., differential ultracentrifugation vs. SEC/gradients vs. immunocapture).⁷⁹ Include orthogonal particle and cargo quantification and normalization strategies. Mitigate lipoprotein co-isolation using apoB depletion and density/size separation. Third, integrated multi-omics and cell-of-origin mapping. Combine lipidomics, proteomics, and small-RNA profiling with robust origin markers and negative controls for contaminants to move from association to mechanism. Fourth, test whether dietary patterns (e.g., fat quality, energy balance and timing) can recalibrate EV profiles in ways that predict or mediate health improvements and assess durability after weight loss or maintenance. Fifth, in humans, prioritize label-based tracer studies (stable isotopes/orthogonal labels), dose–response, and rigorous negative controls to determine true absorption, tissue delivery, and target engagement before inferring systemic effects or clinical utility.

Advances in high-throughput EV characterization coupled with computational modelling and machine learning will accelerate pattern discovery and hypothesis generation. Yet meaningful translation requires that analytical sophistication be matched by methodological discipline. By uniting standardized workflows, mechanistic insights, and clinical endpoints, the field will be better positioned to convert EV biology into actionable nutritional and therapeutic strategies for improving metabolic health.

Author contributions

Conceptualization, S. M.-d. l. P.; investigation, E. M.-P.; resources, S.M.-d. l. P.; writing – original draft preparation, E. M.-P.; writing – review and editing, S. M.-d. l. P. All authors have read and agreed to the published version of the manuscript.

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.

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 publication is part of the project PID2022-138650OA-I00, funded by MICIU/AEI/10.13039/501100011033 and by ERDF/EU. EMP has the benefit of a doctoral fellowship from the Spanish Ministry of Science, Innovation, and Universities (FPU22/01097).

References

1. T. M. Powell-Wiley, P. Poirier, L. E. Burke, J. P. Després, P. Gordon-Larsen, C. J. Lavie, S. A. Lear, C. E. Ndumele, I. J. Neeland, P. Sanders and M. P. St-Onge, Obesity and cardiovascular disease: a scientific statement from the American Heart Association, Circulation, 2021, 143, e984–e1010.
2. G. van Niel, G. D'Angelo and G. Raposo, Shedding light on the cell biology of extracellular vesicles, Nat. Rev. Mol. Cell Biol., 2018, 19, 213–228.
3. V. Suštar, A. Bedina-Zavec, R. Stukelj, M. Frank, E. Ogorevc, R. Janša, K. Mam, P. Veranič and V. Kralj-Iglič, Post-prandial rise of microvesicles in peripheral blood of healthy human donors, Lipids Health Dis., 2011, 10, 47.
4. S. Jamaly, C. Ramberg, R. Olsen, N. Latysheva, P. Webster, T. Sovershaev, S. K. Brækkan and J. B. Hansen, Impact of preanalytical conditions on plasma concentration and size distribution of extracellular vesicles using nanoparticle tracking analysis, Sci. Rep., 2018, 8, 17216.
5. J. J. Vanhie, W. Kim, L. E. Orloff, M. Ngu, N. Collao and M. De Lisio, The role of exercise- and high-fat-diet-induced bone marrow extracellular vesicles in stress hematopoiesis, Front. Physiol., 2022, 13, 1054463.
6. G. Raposo and P. D. Stahl, Extracellular vesicles: a new communication paradigm?, Nat. Rev. Mol. Cell Biol., 2019, 20, 509–510.
7. M. Sheta, E. A. Taha, Y. Lu and T. Eguchi, Extracellular vesicles: new classification and tumor immunosuppression, Biology, 2023, 12, 110.
8. L. Moeinzadeh, I. Razeghian-Jahromi, Z. Zarei-Behjani, Z. Bagheri and M. Razmkhah, Composition, biogenesis, and role of exosomes in tumor development, Stem Cells Int., 2022, 2022, 8392509.
9. P. Kumari, S. S. Wright and V. A. Rathinam, Role of extracellular vesicles in immunity and host defense, Immunol. Invest., 2024, 53, 10–25.
10. J. Jankovičová, P. Sečová, K. Michalková and J. Antalíková, Tetraspanins, more than markers of extracellular vesicles in reproduction, Int. J. Mol. Sci., 2020, 21, 7568.
11. S. Ram, A. Singh, N. Bowler, A. N. Duffy, A. Friedman, C. Fedele, S. Kurtoglu, S. K. Tripathi, K. Wang, A. Hawkins, A. Sayeed, C. P. Goswami, M. L. Thakur, R. V. Iozzo, S. C. Peiper, W. K. Kelly and L. R. Languino, Prostate cancer sheds the αvβ3 integrin in vivo, through exosomes, Matrix Biol., 2019, 77, 41–57.
12. H. C. Chuang, M. H. Chen, Y.-M. Chen, Y. R. Ciou, C. H. Hsueh, C. Y. Tsai and T. H. Tan, Induction of interferon-γ and tissue inflammation by overexpression of eosinophil cationic protein in T cells and exosomes, Arthritis Rheumatol., 2022, 74, 92–104.
13. X. Chen, Y. Zhou and J. Yu, Exosome-like nanoparticles from ginger rhizomes inhibited NLRP3 inflammasome activation, Mol. Pharm., 2019, 16, 2690–2699.
14. S. Ghadami and K. Dellinger, The lipid composition of extracellular vesicles: applications in diagnostics and therapeutic delivery, Front. Mol. Biosci., 2023, 10, 1198044.
15. K. Yuyama, H. Sun, Y. Igarashi, K. Monde, T. Hirase, M. Nakayama and Y. Makino, Immuno-digital invasive cleavage assay for analyzing Alzheimer's amyloid β-bound extracellular vesicles, Alzheimers Res. Ther., 2022, 14, 140.
16. M. Tinè, Y. Padrin, M. Bonato, U. Semenzato, E. Bazzan, M. Conti, M. Saetta, G. Turato and S. Baraldo, Extracellular vesicles (EVs) as crucial mediators of cell–cell interaction in asthma, Int. J. Mol. Sci., 2023, 24, 4645.
17. A. Vishnoi and S. Rani, miRNA biogenesis and regulation of diseases: an updated overview, Methods Mol. Biol., 2023, 2595, 1–12.
18. X. Zhou, M. Su, J. Lu, D. Li, X. Niu and Y. Wang, CD36: the bridge between lipids and tumors, Molecules, 2024, 29, 531.
19. L. Thomas, T. Florio and C. Perez-Castro, Extracellular vesicles loaded miRNAs as potential modulators shared between glioblastoma, and Parkinson's and Alzheimer's diseases, Front. Cell. Neurosci., 2020, 14, 590034.
20. L. Bozzetto, G. Della Pepa, C. Vetrani and A. A. Rivellese, Dietary impact on postprandial lipemia, Front. Endocrinol., 2020, 11, 337.
21. S. Lopez, B. Bermudez, S. Montserrat-de la Paz, R. Abia and F. J. G. Muriana, A microRNA expression signature of the postprandial state in response to a high-saturated-fat challenge, J. Nutr. Biochem., 2018, 57, 45–55.
22. E. C. E. Meessen, M. V. Warmbrunn, M. Nieuwdorp and M. R. Soeters, Human postprandial nutrient metabolism and low-grade inflammation: a narrative review, Nutrients, 2019, 11, 3000.
23. Z. Vázquez-Ruiz, E. Toledo, F. Vitelli-Storelli, L. Goni, V. D. L. O. M. Bes-Rastrollo and M.Á Martínez-González, Effect of dietary phenolic compounds on incidence of cardiovascular disease in the SUN Project: 10 years of follow-up, Antioxidants, 2022, 11, 783.
24. S. Motoyama, Y. Nagahara, M. Sarai, H. Kawai, K. Miyajima, Y. Sato, R. Matsumoto, H. Takahashi, H. Naruse, J. Ishii, Y. Ozaki and H. Izawa, Effect of omega-3 fatty acids on coronary plaque morphology: a serial computed tomography angiography study, Circ. J., 2022, 86, 831–842.
25. K. Kalisz, P. J. Navin, M. Itani, A. K. Agarwal, S. K. Venkatesh and P. S. Rajiah, Multimodality imaging in metabolic syndrome: state-of-the-art review, Radiographics, 2024, 44, e230083.
26. M. Mørk, M. H. Nielsen, R. Bæk, M. M. Jørgensen, S. Pedersen and S. R. Kristensen, Postprandial increase in blood plasma levels of tissue factor-bearing (and other) microvesicles measured by flow cytometry: fact or artifact?, TH Open., 2018, 2, e147–e157.
27. S. Rome and S. Tacconi, High-fat diets: you are what you eat… your extracellular vesicles too!, J. Extracell. Vesicles, 2024, 13, e12382.
28. I. Del Conde, C. N. Shrimpton, P. Thiagarajan and J. A. López, Tissue-factor-bearing microvesicles arise from lipid rafts and fuse with activated platelets to initiate coagulation, Blood, 2005, 106, 1604–1611.
29. N. A. Garcia, H. González-King, E. Grueso, R. Sánchez, A. Martinez-Romero, B. Jávega, J. E. O'Connor, P. J. Simons, A. Handberg and P. Sepúlveda, Circulating exosomes deliver free fatty acids from the bloodstream to cardiac cells: possible role of CD36, PLoS One, 2019, 14, e0217546.
30. D. C. Mantilla-Escalante, M. C. López de las Hazas, J. Gil-Zamorano, L. del Pozo-Acebo, M. C. Crespo, R. Martín-Hernández, A. del Saz, J. Tomé-Carneiro, F. Cardona, I. Cornejo-Pareja, A. García-Ruiz, O. Briand, M. A. Lasunción, F. Visioli and A. Dávalos, Postprandial circulating miRNAs in response to a dietary fat challenge, Nutrients, 2019, 11, 1326.
31. J. Zhang, C. A. Powell, M. K. Kay, R. Sonkar, S. Meruvu and M. Choudhury, Effect of chronic Western diets on non-alcoholic fatty liver of male mice modifying the PPAR-γ pathway via miR-27b-5p regulation, Int. J. Mol. Sci., 2021, 22, 1822.
32. M. Villalva, E. García-Díez, M.-C. López de las Hazas, O. Lo Iacono, J. I. Vicente-Díez, S. García-Cabrera, M. Alonso-Bernáldez, A. Dávalos, M.Á Martín, S. Ramos and J. Pérez-Jiménez, Cocoa–carob blend acute intake modifies miRNAs related to insulin sensitivity in type 2 diabetic subjects: a randomised controlled nutritional trial, Food Funct., 2025, 16, 3211–3226.
33. A. P. Garza, E. Wider-Eberspächer, L. Morton, M. van Ham, É. Pállinger, E. I. Buzás, L. Jänsch and I. R. Dunay, Proteomic analysis of plasma-derived extracellular vesicles: pre- and postprandial comparisons, Sci. Rep., 2024, 14, 23032.
34. M. Di Cesare, P. Perel, S. Taylor, C. Kabudula, H. Bixby, T. A. Gaziano, D. V. McGhie, J. Mwangi, B. Pervan, J. Narula, D. Pineiro and F. J. Pinto, The heart of the world, Glob. Heart, 2024, 19, 11.
35. M. Coelho, T. Oliveira and R. Fernandes, Biochemistry of adipose tissue: an endocrine organ, Arch. Med. Sci., 2013, 9, 191–200.
36. W. P. Cawthorn, E. L. Scheller, B. S. Learman, S. D. Parlee, B. R. Simon, H. Mori, X. Ning, A. J. Bree, B. Schell, D. T. Broome, S. S. Soliman, J. L. DelProposto, C. N. Lumeng, A. Mitra, S. V. Pandit, K. A. Gallagher, J. D. Miller, V. Krishnan, S. K. Hui, M. A. Bredella, P. K. Fazeli, A. Klibanski, M. C. Horowitz, C. J. Rosen and O. A. MacDougald, Bone marrow adipose tissue is an endocrine organ that contributes to increased circulating adiponectin during caloric restriction, Cell Metab., 2014, 20, 368–375.
37. J. Amosse, M. Durcin, M. Malloci, L. Vergori, A. Fleury, F. Gagnadoux, S. Dubois, G. Simard, J. Boursier, O. Hue, M. C. Martinez, R. Andriantsitohaina and S. L. Lay, Phenotyping of circulating extracellular vesicles (EVs) in obesity identifies large EVs as functional conveyors of macrophage migration inhibitory factor, Mol. Metab., 2018, 18, 134–142.
38. K. Sumaiya, D. Langford, K. Natarajaseenivasan and S. Shanmughapriya, Macrophage migration inhibitory factor (MIF): a multifaceted cytokine regulated by genetic and physiological strategies, Pharmacol. Ther., 2022, 233, 108024.
39. S. Li, S. H. A. Raza, C. Zhao, G. Cheng and L. Zan, Overexpression of PLIN1 promotes lipid metabolism in bovine adipocytes, Animals, 2020, 10, 1944.
40. V. Kumar, S. Kiran, S. Kumar and U. P. Singh, Extracellular vesicles in obesity and its associated inflammation, Int. Rev. Immunol., 2022, 41, 30–44.
41. T. Camino, N. Lago-Baameiro, S. B. Bravo, A. Molares-Vila, A. Sueiro, I. Couto, J. Baltar, F. F. Casanueva and M. Pardo, Human obese white adipose tissue sheds depot-specific extracellular vesicles and reveals candidate biomarkers for monitoring obesity and its comorbidities, Transl. Res., 2022, 239, 85–102.
42. S. C. Ferrante, E. P. Nadler, D. K. Pillai, M. J. Hubal, Z. Wang, J. M. Wang, H. Gordish-Dressman, E. Koeck, S. Sevilla, A. A. Wiles and R. J. Freishtat, Adipocyte-derived exosomal miRNAs: a novel mechanism for obesity-related disease, Pediatr. Res., 2015, 77, 447–454.
43. Y. Pan, X. Hui, R. L. C. Hoo, D. Ye, C. Y. C. Chan, T. Feng, Y. Wang, K. S. L. Lam and A. Xu, Adipocyte-secreted exosomal microRNA-34a inhibits M2 macrophage polarization to promote obesity-induced adipose inflammation, J. Clin. Invest., 2019, 129, 834–849.
44. D. Zhang, X. Yao, Y. Teng, T. Zhao, L. Lin, Y. Li, H. Shang, Y. Jin and Q. Jin, Adipocytes-derived exosomal microRNA-1224 inhibits M2 macrophage polarization in obesity-induced adipose tissue inflammation via MSI2-mediated Wnt/β-catenin axis, Mol. Nutr. Food Res., 2022, 66, e2100889.
45. Z. Xie, X. Wang, X. Liu, H. Du, C. Sun, X. Shao, J. Tian, X. Gu, H. Wang, J. Tian and B. Yu, Adipose-derived exosomes exert proatherogenic effects by regulating macrophage foam cell formation and polarization, J. Am. Heart Assoc., 2018, 7, e007442.
46. A. Giannella, C. M. Radu, L. Franco, E. Campello, P. Simioni, A. Avogaro, S. Vigili de Kreutzenberg and G. Ceolotto, Circulating levels and characterization of microparticles in patients with different degrees of glucose tolerance, Cardiovasc. Diabetol., 2017, 16, 118.
47. F. Puhm, E. Boilard and K. R. Machlus, Platelet extracellular vesicles: beyond the blood, Arterioscler. Thromb. Vasc. Biol., 2021, 41, 87–96.
48. B. Hosseinkhani, S. Kuypers, N. M. S. van den Akker, D. G. M. Molin and L. Michiels, Extracellular vesicles work as a functional inflammatory mediator between vascular endothelial cells and immune cells, Front. Immunol., 2018, 9, 1789.
49. Y. Ji, Z. Gong, R. Liang, D. Wu, W. Sun, X. Luo, Y. Yan, J. Lu, J. Wang and H. Wang, Extracellular vesicle-mediated miR-155 from visceral adipocytes induces skeletal muscle dysplasia in obesity, Cells, 2025, 14, 1302.
50. W. Ying, M. Riopel, G. Bandyopadhyay, Y. Dong, A. Birmingham, J. B. Seo, J. M. Ofrecio, J. Wollam, A. Hernandez-Carretero, W. Fu, P. Li and J. M. Olefsky, Adipose tissue macrophage-derived exosomal miRNAs can modulate in vivo and in vitro insulin sensitivity, Cell, 2017, 171, 372–384.
51. N. Akbar, V. Azzimato, R. P. Choudhury and M. Aouadi, Extracellular vesicles in metabolic disease, Diabetologia, 2019, 62, 2179–2187.
52. L. F. Heinrich, D. K. Andersen, M. E. Cleasby and C. Lawson, Long-term high fat feeding of rats results in increased numbers of circulating microvesicles with pro-inflammatory effects on endothelial cells, Br. J. Nutr., 2015, 113, 1704–1711.
53. E. Campello, E. Zabeo, C. M. Radu, L. Spiezia, M. Foletto, L. Prevedello, S. Gavasso, C. Bulato, R. Vettor and P. Simioni, Dynamics of circulating microparticles in obesity after weight loss, Intern. Emerg. Med., 2016, 11, 695–702.
54. T. Murakami, H. Horigome, K. Tanaka, Y. Nakata, K. Ohkawara, Y. Katayama and A. Matsui, Impact of weight reduction on production of platelet-derived microparticles and fibrinolytic parameters in obesity, Thromb. Res., 2007, 119, 45–53.
55. A. B. Thrush, G. Antoun, M. Nikpay, D. A. Patten, C. DeVlugt, J.-F. Mauger, B. L. Beauchamp, P. Lau, R. Reshke, É. Doucet, P. Imbeault, R. Boushel, D. Gibbings, J. Hager, A. Valsesia, R. S. Slack, O. Y. Al-Dirbashi, R. Dent, R. McPherson and M.-E. Harper, Diet-resistant obesity is characterized by a distinct plasma proteomic signature and impaired muscle fiber metabolism, Int. J. Obes., 2018, 42, 353–362.
56. A. Eguchi, M. Lazic, A. M. Armando, S. A. Phillips, R. Katebian, S. Maraka, O. Quehenberger, D. D. Sears and A. E. Feldstein, Circulating adipocyte-derived extracellular vesicles are novel markers of metabolic stress, J. Mol. Med., 2016, 94, 1241–1253.
57. H. Aswad, A. Forterre, O. P. B. Wiklander, G. Vial, E. Danty-Berger, A. Jalabert, A. Lamazière, E. Meugnier, S. Pesenti, C. Ott, K. Chikh, S. El-Andaloussi, H. Vidal, E. Lefai, J. Rieusset and S. Rome, Exosomes participate in the alteration of muscle homeostasis during lipid-induced insulin resistance in mice, Diabetologia, 2014, 57, 2155–2164.
58. M. Durcin, A. Fleury, E. Taillebois, G. Hilairet, Z. Krupova, C. Henry, S. Truchet, M. Trötzmüller, H. Köfeler, G. Mabilleau, O. Hue, R. Andriantsitohaina, P. Martin and S. L. Lay, Characterisation of adipocyte-derived extracellular vesicle subtypes identifies distinct protein and lipid signatures for large and small extracellular vesicles, J. Extracell. Vesicles, 2017, 6, 1305677.
59. A. Kumar, K. Sundaram, J. Mu, G. W. Dryden, M. K. Sriwastva, C. Lei, L. Zhang, X. Qiu, F. Xu, J. Yan, X. Zhang, J. W. Park, M. L. Merchant, H. C. L. Bohler, B. Wang, S. Zhang, C. Qin, Z. Xu, X. Han, C. J. McClain, Y. Teng and H.-G. Zhang, High-fat diet-induced upregulation of exosomal phosphatidylcholine contributes to insulin resistance, Nat. Commun., 2021, 12, 213.
60. Q. Guo, K. Furuta, F. Lucien, L. H. Gutierrez Sanchez, P. Hirsova, A. Krishnan, A. Kabashima, K. D. Pavelko, B. Madden, H. Alhuwaish, Y. Gao, A. Revzin and S. H. Ibrahim, Integrin β1-enriched extracellular vesicles mediate monocyte adhesion and promote liver inflammation in murine NASH, J. Hepatol., 2019, 71, 1193–1205.
61. H. P. Hirsova, S. H. Ibrahim, A. Krishnan, V. K. Verma, S. F. Bronk, N. W. Werneburg, M. R. Charlton, V. H. Shah, H. Malhi and G. J. Gores, Lipid-induced signaling causes release of inflammatory extracellular vesicles from hepatocytes, Gastroenterology, 2016, 150, 956–967.
62. C. Yan, X. Tian, J. Li, D. Liu, D. Ye, Z. Xie, Y. Han and M.-H. Zou, A high-fat diet attenuates AMPK α1 in adipocytes to induce exosome shedding and nonalcoholic fatty liver development in vivo, Diabetes, 2021, 70, 577–588.
63. Z. Zhao, L. Zhong, P. Li, K. He, C. Qiu, L. Zhao and J. Gong, Cholesterol impairs hepatocyte lysosomal function causing M1 polarization of macrophages via exosomal miR-122–5p, Exp. Cell Res., 2020, 387, 111738.
64. M. Párrizas, L. Brugnara, Y. Esteban, A. González-Franquesa, S. Canivell, S. Murillo, E. Gordillo-Bastidas, R. Cussó, J. A. Cadefau, P. M. García-Roves, J.-M. Servitja and A. Novials, Circulating miR-192 and miR-193b are markers of prediabetes and are modulated by an exercise intervention, J. Clin. Endocrinol. Metab., 2015, 100, E407–E415.
65. M. van de Bunt, K. J. Gaulton, L. Parts, I. Moran, P. R. Johnson, C. M. Lindgren, J. Ferrer, A. L. Gloyn and M. I. McCarthy, The miRNA profile of human pancreatic islets and beta-cells and relationship to type 2 diabetes pathogenesis, PLoS One, 2013, 8, e55272.
66. L. Sun, H. Xie, M. A. Mori, R. Alexander, B. Yuan, S. M. Hattangadi, Q. Liu, C. R. Kahn and H. F. Lodish, MiR-193b-365 is essential for brown fat differentiation, Nat. Cell Biol., 2011, 13, 958–965.
67. P. Manning, P. E. Munasinghe, J. B. Papannarao, A. R. Gray, W. Sutherland and R. Katare, Acute weight loss restores dysregulated circulating microRNAs in individuals who are obese, J. Clin. Endocrinol. Metab., 2019, 104, 1239–1248.
68. D. C. Mantilla-Escalante, M.-C. López de Las Hazas, M. C. Crespo, R. Martín-Hernández, J. Tomé-Carneiro, L. Del Pozo-Acebo, J. Salas-Salvadó, M. Bulló and A. Dávalos, Mediterranean diet enriched in extra-virgin olive oil or nuts modulates circulating exosomal non-coding RNAs, Eur. J. Nutr., 2021, 60, 4279–4293.
69. M. Thibonnier and C. Esau, Metabolic benefits of microRNA-22 inhibition, Nucleic Acid Ther., 2020, 30, 104–116.
70. M.Á Ávila-Gálvez, M. Romo-Vaquero, C. Mazarío-Gárgoles, J. Tomé-Carneiro, M.-C. López de Las Hazas, A. Dávalos, M. V. Selma, A. González-Sarrías and J. C. Espín, Oral delivery of ellagic acid encapsulated in milk exosomes: sex-based differences in bioavailability, urolithin production, and gut microbiota modulation, Mol. Nutr. Food Res., 2025, 69, e70104.
71. F. Perut, L. Roncuzzi, S. Avnet, A. Massa, N. Zini, S. Sabbadini, F. Giampieri, B. Mezzetti and N. Baldini, Strawberry-derived exosome-like nanoparticles prevent oxidative stress in human mesenchymal stromal cells, Biomolecules, 2021, 11, 87.
72. N. Baldini, E. Torreggiani, L. Roncuzzi, F. Perut, N. Zini and S. Avnet, Exosome-like nanovesicles isolated from Citrus limon L. exert antioxidative effect, Curr. Pharm. Biotechnol., 2018, 19, 877–885.
73. M. K. Kim, Y. C. Choi, S. H. Cho, J. S. Choi and Y. W. Cho, The antioxidant effect of small extracellular vesicles derived from Aloe vera peels for wound healing, Tissue Eng. Regener. Med., 2021, 18, 561–571.
74. W. J. Zhao, Y. P. Bian, Q. H. Wang, F. Yin, L. Yin, Y. L. Zhang and J. H. Liu, Blueberry-derived exosome-like nanoparticles ameliorate nonalcoholic fatty liver disease by attenuating mitochondrial oxidative stress, Acta Pharmacol. Sin., 2022, 43, 645–658.
75. J. Xiao, S. Feng, X. Wang, K. Long, Y. Luo, Y. Wang, J. Ma, Q. Tang, L. Jin, X. Li and M. Li, Identification of exosome-like nanoparticle-derived microRNAs from 11 edible fruits and vegetables, PeerJ, 2018, 6, e5186.
76. X. Zhuang, Y. Teng, A. Samykutty, J. Mu, Z. Deng, L. Zhang, P. Cao, Y. Rong, J. Yan, D. Miller and H.-G. Zhang, Grapefruit-derived nanovectors delivering therapeutic miR-17 through an intranasal route inhibit brain tumor progression, Mol. Ther., 2016, 24, 96–105.
77. J. Shang, J. Ning, X. Bai, X. Cao, X. Yue and M. Yang, Identification and analysis of miRNAs expression profiles in human, bovine, and donkey milk exosomes, Int. J. Biol. Macromol., 2023, 252, 126321.
78. M.Á Ávila-Gálvez, B. Garay-Mayol, J. A. Giménez-Bastida, M. D. C. López de las Hazas, C. Mazarío-Gárgoles, M. A. Brito, A. Dávalos, J. C. Espín and A. González-Sarrías, Enhanced brain delivery and antiproliferative activity of resveratrol using milk-derived exosomes, J. Agric. Food Res., 2024, 18, 101370.
79. J. A. Welsh, D. C. I. Goberdhan, L. O'Driscoll, E. I. Buzás, C. Blenkiron, B. Bussolati, H. Cai, D. Di Vizio, T. A. P. Driedonks and U. Erdbrügger, et al., Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches, J. Extracell. Vesicles, 2024, 13, e12404.

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