Journal
JOURNAL OF LIPID RESEARCH
Volume 51, Issue 3, Pages 554-563Publisher
ELSEVIER
DOI: 10.1194/jlr.M000976
Keywords
hepatic steatosis; lipodystrophy; perilipin family; lipin; lipid droplet
Categories
Funding
- National Institutes of Health [DK078187, GM23750, DK083163]
- American Diabetes Association [7-06-JF-69]
- National Heart, Lung and Blood Institute [T32 HL-007275]
- Digestive Diseases Research Core Center [P30 DK52574]
- Clinical Nutrition Research Unit at Washington University School of Medicine [P30 DK56341]
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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, A. M., E. M. Brunt, Z. Chen, N. Viswakarma, J. K. Reddy, N. E. Wolins, and B. N. Finck. Dynamic and differential regulation of proteins that coat lipid droplets in fatty liver dystrophic mice. J. Lipid Res. 2010. 51: 554-563.
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