Inhibition of soluble epoxide hydrolase ameliorates hyperhomocysteinemia-induced hepatic steatosis by enhancing β-oxidation of fatty acid in mice

American Journal of Physiology. Gastrointestinal and Liver Physiology
Liu YaoYi Zhu

Abstract

Hepatic steatosis is the beginning phase of nonalcoholic fatty liver disease, and hyperhomocysteinemia (HHcy) is a significant risk factor. Soluble epoxide hydrolase (sEH) hydrolyzes epoxyeicosatrienoic acids (EETs) and other epoxy fatty acids, attenuating their cardiovascular protective effects. However, the involvement of sEH in HHcy-induced hepatic steatosis is unknown. The current study aimed to explore the role of sEH in HHcy-induced lipid disorder. We fed 6-wk-old male mice a chow diet or 2% (wt/wt) high-metnionine diet for 8 wk to establish the HHcy model. A high level of homocysteine induced lipid accumulation in vivo and in vitro, which was concomitant with the increased activity and expression of sEH. Treatment with a highly selective specific sEH inhibitor (0.8 mg·kg-1·day-1 for the animal model and 1 μM for cells) prevented HHcy-induced lipid accumulation in vivo and in vitro. Inhibition of sEH activated the peroxisome proliferator-activated receptor-α (PPAR-α), as evidenced by elevated β-oxidation of fatty acids and the expression of PPAR-α target genes in HHcy-induced hepatic steatosis. In primary cultured hepatocytes, the effect of sEH inhibition on PPAR-α activation was further confirmed by a marked increase in ...Continue Reading

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Citations

May 14, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Carlos A Trindade-da-SilvaMarcelo H Napimoga
Mar 19, 2020·International Journal of Molecular Sciences·Can G LeineweberKarsten H Weylandt
Sep 7, 2020·Pharmacology & Therapeutics·Anna FishbeinDipak Panigrahy
Jul 2, 2021·Nutrition & Metabolism·Christine BrüttingGabriele I Stangl
Dec 29, 2020·Journal of Medicinal Chemistry·Cheng-Peng SunXiao-Chi Ma

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Methods Mentioned

BETA
PCR
transfection

Software Mentioned

GraphPad Prism
ImageJ

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