Enoyl coenzyme A hydratase 1 protects against high-fat-diet-induced hepatic steatosis and insulin resistance

Biochem Biophys Res Commun. 2018 May 15;499(3):403-409. doi: 10.1016/j.bbrc.2018.03.052. Epub 2018 Apr 3.

Abstract

Metabolic disorders, including obesity, non-alcoholic fatty liver disease (NAFLD), metabolic syndrome and diabetes, are complex and progressive diseases. Enoyl coenzyme A hydratase 1 (Ech1) is an enzyme that participates in mitochondrial fatty acid β-oxidation; however, little is known regarding the significance of Ech1 in the pathogenesis of metabolic disorders. Here, we report that high-fat-diet (HFD)-induced and genetic obesity could increase Ech1 expression in mouse liver. The overexpression of Ech1 using adeno-associated virus (AAV2/8) ameliorated HFD-induced liver lipid accumulation and accompanying liver injury. Additionally, Ech1 overexpression resulted in improved dyslipidemia and insulin resistance in HFD-fed mice. Further, the studies revealed that Ech1 could directly inhibit lipogenesis gene expressions and attenuate the insulin pathway induced by an HFD. Together, our results demonstrate that Ech1 protects against HFD-induced hepatic steatosis and insulin resistance and that its inhibitory effects on lipogenesis and insulin signaling may partly explain its role in metabolic disorders.

Keywords: Ech1; High-fat diet; Insulin resistance; Metabolic disorder; Steatosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbon-Carbon Double Bond Isomerases / metabolism*
  • Diet, High-Fat
  • Dyslipidemias / complications
  • Dyslipidemias / enzymology
  • Dyslipidemias / pathology
  • Insulin / metabolism
  • Insulin Resistance*
  • Lipogenesis
  • Liver / injuries
  • Liver / metabolism
  • Liver / pathology
  • Mice, Inbred C57BL
  • Non-alcoholic Fatty Liver Disease / enzymology*
  • Non-alcoholic Fatty Liver Disease / pathology
  • Non-alcoholic Fatty Liver Disease / prevention & control*
  • Obesity / enzymology
  • Obesity / genetics
  • Signal Transduction

Substances

  • Insulin
  • Carbon-Carbon Double Bond Isomerases
  • delta(3,5),delta(2,4)-dienoyl-CoA isomerase