Inhibition of Soluble Epoxide Hydrolase Ameliorates Hyperhomocysteinemia-Induced Hepatic Steatosis by Enhancing β-oxidation of Fatty Acid in Mice.

Inhibition of Soluble Epoxide Hydrolase Ameliorates Hyperhomocysteinemia-Induced Hepatic Steatosis by Enhancing β-oxidation of Fatty Acid in Mice. Am J Physiol Gastrointest Liver Physiol. 2019 Feb 21;: Authors: Yao L, Cao B, Cheng Q, Cai W, Ye C, Liang J, Liu W, Tan L, Yan M, Li B, He J, Hwang SH, Zhang X, Wang C, Ai D, Hammock BD, Zhu Y Abstract Hepatic steatosis is the beginning phase of non-alcoholic 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-week-old male mice a chow diet or 2% (wt/wt) high methione diet for 8 weeks 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/day for the animal model and 1 μM for cells) prevented HHcy-induced lipid accumulation in vivo and in vitro. Inhibition of sEH activated peroxisome proliferator-activated receptor-α (PPARα), as evidenced by elevated β-oxidation of fatty acids and the expression of PPARα target genes in HHcy-induced hepatic s...
Source: Am J Physiol Gastroi... - Category: Gastroenterology Authors: Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research