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- W3016429938 abstract "Hepatic steatosis is characterized by excessive accumulation of triglyceride (TG). Mitochondrial membrane uncoupling proteins (UCPs) are potential targets for obesity treatment, given their ability to dissipate energy as heat. Previous studies in our lab have indicated that the omega-3 polyunsaturated fatty acid, eicosapentaenoic acid (EPA), reduced obesity, inflammation and hepatic steatosis, and upregulated brown adipose tissue UCP1 protein in high fat (HF) fed mice housed at ambient temperature (22–23°C). However, EPA-mediated improvements were attenuated and were independent of UCP1 when mice were housed in a thermoneutral environment (28–30°C). Thus, the objective of this work is to determine mechanisms of EPA-mediated improvements in liver steatosis in UCP1 Knockout (KO) mice. Wild type (WT) and UCP1-KO B6 mice were fed a HF diet with 36 g/kg AlaskOmega, 800mg/g fish oil of EPA (WT-EPA, KO-EPA) or without EPA (WT-HF, KO-HF) for 14 weeks. Mice were metabolically phenotyped during the feeding period, and histology and molecular analyses were performed in the liver after euthanasia. The KO-HF group were highest in body weight, while KO-HF, WT-HF and WT-EPA were comparable. Surprisingly, EPA attenuated weight gain in the KO-EPA group compared to KO-HF. Further, liver TG levels were significantly reduced in the KO-EPA group compared to the KO-HF. Consistent with this finding, EPA upregulated fatty acid beta-oxidation markers only in the KO-EPA group, indicated by significant increases in peroxisome proliferator activated receptor-alpha (Ppara) and carnitine palmitoyltransferase (Cpt) 1a compared to KO-HF. In conclusion, EPA rescued the detrimental effects of UCP1 deficiency in the livers of HF fed mice in a thermoneutral environment. Further studies are ongoing to dissect mechanistic basis for UCP1-independent beneficial effects of EPA in liver steatosis. Our promising findings warrant further EPA supplementation studies in humans with obesity, given the limited activity of brown adipose tissue and downregulation of UCP1 in this population. Support or Funding Information Funded by NIH/NCCIH grant #R15AT008879-01A1 (N.M.M.)" @default.
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- W3016429938 date "2020-04-01" @default.
- W3016429938 modified "2023-10-18" @default.
- W3016429938 title "Eicosapentaenoic Acid Reduces Hepatic Steatosis Independently of UCP1" @default.
- W3016429938 doi "https://doi.org/10.1096/fasebj.2020.34.s1.00343" @default.
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