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

Angela M. Hall, Elizabeth M. Brunt, Zhouji Chen, Navin Viswakarma, Janardan K. Reddy, Nathan E. Wolins, Brian N. Finck

Research output: Contribution to journalArticle

34 Scopus citations

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 (fl d) 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 fl d liver but returned to normal by P17. However, the changes in perilipin-2 and perilipin-5 protein content in fl d 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 fl d mouse liver. Surprisingly, levels of peroxisome proliferator-activated receptor, which is known to regulate Cide expression, were unchanged in fl d mice. However, sterol-regulatory element binding protein 1 (SREBP-1) was activated in fl d liver and CideA was revealed as a new direct target gene of SREBP-1. In summary, LDP content is markedly increased in liver of fl d 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.

Original languageEnglish
Pages (from-to)554-563
Number of pages10
JournalJournal of lipid research
Volume51
Issue number3
DOIs
StatePublished - Mar 1 2010

Keywords

  • Hepatic steatosis
  • Lipid droplet
  • Lipin
  • Lipodystrophy
  • Perilipin family

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