Further evidence for the involvement of mitochondrial aquaporin-8 in hepatocyte lipid synthesis

Biochimie. 2021 Sep:188:16-19. doi: 10.1016/j.biochi.2021.01.008. Epub 2021 Jan 23.

Abstract

We recently provided evidence suggesting that mitochondrial aquaporin-8 (mtAQP8), a channel protein able to conduct H2O2, is involved in the modulation of hepatocyte cholesterogenesis. To expand that study, we cultured human hepatocyte-derived Huh-7 cells in medium with lipoprotein-deficient serum (LPDS) to induce the de novo synthesis of cholesterol and fatty acids. We found that LPDS induced mtAQP8 expression and that AQP8 gene silencing significantly down-regulated the LPDS-induced synthesis of cholesterol and fatty acids as well as the expression of the corresponding key biosynthetic enzymes, 3-hydroxy-3-methylglutaryl-CoA reductase and fatty acid synthase. Our data further support a regulatory role of mtAQP8 in hepatocyte lipid homeostasis.

Keywords: Cholesterol; Fatty acid synthase; Fatty acids; HMG-CoA reductase; Huh-7 cells; Mitochondrial aquaporin-8.

MeSH terms

  • Aquaporins / genetics*
  • Aquaporins / metabolism*
  • Cell Line, Tumor
  • Cholesterol / biosynthesis
  • Fatty Acid Synthase, Type I / metabolism
  • Fatty Acids / biosynthesis
  • Gene Silencing
  • Hepatocytes / metabolism*
  • Homeostasis
  • Humans
  • Hydroxymethylglutaryl CoA Reductases / metabolism
  • Lipogenesis / physiology*
  • Lipoproteins / deficiency
  • Mitochondria / metabolism*

Substances

  • Aquaporins
  • Fatty Acids
  • Lipoproteins
  • aquaporin 8
  • Cholesterol
  • Hydroxymethylglutaryl CoA Reductases
  • FASN protein, human
  • Fatty Acid Synthase, Type I