Dynamic and differential regulation of proteins that coat lipid droplets in fatty liver dystrophic mice

J Lipid Res. 2010 Mar;51(3):554-63. doi: 10.1194/jlr.M000976. Epub 2009 Sep 11.

Abstract

Lipid droplet proteins (LDPs) coat the surface of triglyceride-rich lipid droplets and regulate their formation and lipolysis. We profiled hepatic LDP expression in fatty liver dystrophic (fld) mice, a unique model of neonatal hepatic steatosis that predictably resolves between postnatal day 14 (P14) and P17. Western blotting revealed that perilipin-2/ADRP and perilipin-5/OXPAT were markedly increased in steatotic fld liver but returned to normal by P17. However, the changes in perilipin-2 and perilipin-5 protein content in fld mice were exaggerated compared with relatively modest increases in corresponding mRNAs encoding these proteins, a phenomenon likely mediated by increased protein stability. Conversely, cell death-inducing DFFA-like effector (Cide) family genes were strongly induced at the level of mRNA expression in steatotic fld mouse liver. Surprisingly, levels of peroxisome proliferator-activated receptor gamma, which is known to regulate Cide expression, were unchanged in fld mice. However, sterol-regulatory element binding protein 1 (SREBP-1) was activated in fld liver and CideA was revealed as a new direct target gene of SREBP-1. In summary, LDP content is markedly increased in liver of fld mice. However, whereas perilipin-2 and perilipin-5 levels are primarily regulated posttranslationally, Cide family mRNA expression is induced, suggesting that these families of LDP are controlled at different regulatory checkpoints.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins
  • Fatty Liver / complications*
  • Fatty Liver / metabolism*
  • Fatty Liver / pathology
  • Female
  • Gene Expression Regulation
  • Lipid Metabolism*
  • Lipids / chemistry*
  • Lipodystrophy / complications*
  • Lipodystrophy / metabolism*
  • Lipodystrophy / pathology
  • Liver / metabolism
  • Liver / pathology
  • Mice
  • PPAR gamma / metabolism
  • Perilipin-1
  • Phenotype
  • Phosphoproteins / metabolism
  • Protein Stability
  • Proteins / chemistry
  • Proteins / genetics
  • Proteins / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sterol Regulatory Element Binding Protein 1 / metabolism
  • Time Factors

Substances

  • Carrier Proteins
  • Lipids
  • PPAR gamma
  • Perilipin-1
  • Phosphoproteins
  • Proteins
  • RNA, Messenger
  • Srebf1 protein, mouse
  • Sterol Regulatory Element Binding Protein 1