Dynamic and differential regulation of proteins that coat lipid droplets in fatty liver dystrophic mice.
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.
Hall
Angela M
AM
Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Brunt
Elizabeth M
EM
Chen
Zhouji
Z
Viswakarma
Navin
N
Reddy
Janardan K
JK
Wolins
Nathan E
NE
Finck
Brian N
BN
D000818:Animals; D002352:Carrier Proteins; D005234:Fatty Liver / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry*; D008060:Lipodystrophy / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism; D000070778:Perilipin-1; D010641:Phenotype; D010750:Phosphoproteins / Q000378:metabolism; D055550:Protein Stability; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D013997:Time Factors
D002352:Carrier Proteins; D008055:Lipids; D047495:PPAR gamma; D000070778:Perilipin-1; D010750:Phosphoproteins; D011506:Proteins; D012333:RNA, Messenger; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1