Depletion of Rab32 decreases intracellular lipid accumulation and induces lipolysis through enhancing ATGL expression in hepatocytes

Biochem Biophys Res Commun. 2016 Mar 18;471(4):492-6. doi: 10.1016/j.bbrc.2016.02.047. Epub 2016 Feb 13.

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a disease caused by the accumulation of lipids in hepatocytes. To date, however, the pathogenesis of NAFLD is still unclear. Recent studies have shown that Rab GTPases, a major protein family in vesicle trafficking, are associated with intracellular lipid accumulation. Here, we show that Rab32, the only Rab GTPase located in mitochondria, participates in hepatic steatosis. Ablation of Rab32 can decrease intracellular lipid accumulation in hepatocytes (HepG2, L02). Further studying the possible mechanism, we found that knockdown of Rab32 can enhance lipolysis instead of lipogenesis via inducing the expression of adipose triglyceride lipase (ATGL), a key enzyme on the surface of lipid droplets which has been proved to be significant in controlling intracellular lipid accumulation. Co-immunoprecipitation shows that Rab32 and ATGL are not directly associated. These findings suggest that knockdown of Rab32 indirectly affects lipolysis through increasing the expression of ATGL. Taken together, our study reveals that Rab32 can participate in regulating intracellular lipid accumulation and that knockdown of Rab32 can decrease intracellular lipid accumulation in hepatocytes. We also demonstrated that ablation of Rab32 can induce intracellular lipolysis by enhancing the expression of ATGL.

Keywords: ATGL; Lipolysis; Rab32.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Knockdown Techniques
  • Hep G2 Cells / metabolism
  • Hepatocytes / metabolism*
  • Humans
  • Lipase / genetics
  • Lipase / metabolism*
  • Lipid Metabolism*
  • Lipolysis / physiology*
  • Non-alcoholic Fatty Liver Disease / metabolism
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / metabolism*

Substances

  • Lipase
  • PNPLA2 protein, human
  • Rab32 protein, human
  • rab GTP-Binding Proteins