PKCδ regulates hepatic triglyceride accumulation and insulin signaling in Lepr(db/db) mice

Biochem Biophys Res Commun. 2014 Aug 8;450(4):1619-25. doi: 10.1016/j.bbrc.2014.07.048. Epub 2014 Jul 15.

Abstract

PKCδ has been linked to key pathophysiological features of non-alcoholic fatty liver disease (NAFLD). Yet, our knowledge of PKCδ's role in NAFLD development and progression in obese models is limited. PKCδ(-/-)/Lepr(db)(/)(db) mice were generated to evaluate key pathophysiological features of NAFLD in mice. Hepatic histology, oxidative stress, apoptosis, gene expression, insulin signaling, and serum parameters were analyzed in Lepr(db)(/)(db) and PKCδ(-/-)/Lepr(db)(/)(db) mice. The absence of PKCδ did not abrogate the development of obesity in Lepr(db)(/)(db) mice. In contrast, serum triglyceride levels and epididymal white adipose tissue weight normalized to body weight were reduced in PKCδ(-/-)/Lepr(db)(/)(db) mice compared Lepr(db)(/)(db) mice. Analysis of insulin signaling in mice revealed that hepatic Akt and GSK3β phosphorylation were strongly stimulated by insulin in PKCδ(-/-)/Lepr(db)(/)(db) compared Lepr(db)(/)(db) mice. PKCδ may be involved in the development of obesity-associated NAFLD by regulating hepatic lipid metabolism and insulin signaling.

Keywords: Insulin resistance; Obesity; Oxidative stress; Steatosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight
  • Fatty Liver / metabolism
  • Gene Expression
  • Insulin / metabolism*
  • Lipid Metabolism / genetics
  • Liver / metabolism*
  • Mice
  • Organ Size
  • Oxidative Stress
  • Polymerase Chain Reaction
  • Protein Kinase C-delta / metabolism*
  • Signal Transduction*
  • Triglycerides / metabolism*

Substances

  • Insulin
  • Triglycerides
  • Protein Kinase C-delta