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Long-Chain Polyunsaturated Fatty Acids and Extensively Hydrolyzed Casein Induce Browning in a Ucp-1 Reporter Mouse Model of Obesity


Browning in adipose tissues, which can be affected by diet, may mitigate detrimental effects of adiposity and improve longer term metabolic health. Here, browning inducing effects of long-chain polyunsaturated fatty acids e.g. arachidonic acid (ARA)/docosahexaenoic acid (DHA) and extensively hydrolyzed casein (eHC) were investigated in uncoupling protein 1 (Ucp-1) reporter mice. To address overall functionality their potential role in supporting a healthy metabolic profile under obesogenic dietary challenges later in life was evaluated. At weaning Ucp1+/LUC reporter mice were fed a control low fat diet (LFD) with or without ARA+DHA, eHC, or eHC+ARA+DHA for 8 weeks until week 12 after which interventions continued for another 12 weeks under a high-fat diet (HFD) challenge. Serology (metabolic responses and inflammation), in vivo and ex vivo luciferase activity was determined, meantime browning-related proteins UCP-1 and genes peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), PR domain containing 16 (PRDM16) and Ucp-1 were examined. ARA+DHA, eHC or their combination reduced body weight gain and adipose tissue weight compared to HFD mice. Interventions induced Ucp-1 expression in adipose tissues prior to and during HFD exposure. Ucp-1 induction was accompanied by higher PGC1a and PRDM16 expression. Glucose tolerance and insulin sensitivity were improved coinciding with lower serum cholesterol, triglycerides, free fatty acids, insulin, leptin, resistin, fibroblast growth factor 21, alanine aminotransferase, aspartate aminotransferase and higher adiponectin than the HFD group. HFD-associated increased systemic (IL-1β and TNF-α), and adipose tissue inflammation (F4/80, IL-1β, TNF-α, IL-6) was reduced. Studies in a Ucp-1 reporter mouse model revealed that early intervention with ARA/DHA and eHC improves metabolic flexibility and attenuates obesity during HFD challenge later in life. Increased browning is suggested as, at least part of, the underlying mechanism.

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Publication details

The article was received on 20 Nov 2017, accepted on 06 Mar 2018 and first published on 08 Mar 2018

Article type: Paper
DOI: 10.1039/C7FO01835E
Citation: Food Funct., 2018, Accepted Manuscript
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    Long-Chain Polyunsaturated Fatty Acids and Extensively Hydrolyzed Casein Induce Browning in a Ucp-1 Reporter Mouse Model of Obesity

    L. Mao, J. Lei, M. H. Schoemaker, B. Ma, Y. Zhong, T. T. Lambers, E. A.F Van Tol, Y. Zhou, T. Nie and D. Wu, Food Funct., 2018, Accepted Manuscript , DOI: 10.1039/C7FO01835E

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