15644454

pubmed:Citation

6

Peroxisome proliferator-activated receptor-gamma (PPARgamma) is considered to be one of the master regulators of adipocyte differentiation. PPARgamma2 is abundantly expressed in mature adipocytes and is elevated in the livers of animals that develop fatty livers. The aim of this study was to determine the ability of PPARgamma2 to induce lipid accumulation in hepatocytes and to delineate molecular mechanisms driving this process. The hepatic cell line AML-12 was used to generate a cell line stably expressing PPARgamma2. Oil Red O staining revealed that PPARgamma2 induces lipid accumulation in hepatocytes. This phenotype is accompanied by a selective upregulation of several adipogenic and lipogenic genes including adipose differentiation-related protein (ADRP), adipocyte fatty acid-binding protein 4, sterol regulatory element-binding protein-1 (SREBP-1), fatty acid synthase (FAS), and acetyl-CoA carboxylase, genes whose expression levels are known to increase in steatotic livers of ob/ob mice. Furthermore, the PPARgamma2-regulated induction of both SREBP-1 and FAS parallels an increase in de novo triacylglycerol synthesis in hepatocytes. Triacylglycerol synthesis and lipid accumulation are further enhanced by culturing hepatocytes with troglitazone in the absence of exogenous lipids. These results correspond with an increase in the lipid droplet protein, ADRP, and the data demonstrate that ADRP functions to coat lipid droplets in hepatocytes as observed by confocal microscopy. Taken together, these observations propose a role for PPARgamma2 as an inducer of steatosis in hepatocytes and suggest that this phenomenon occurs through an induction of pathways regulating de novo lipid synthesis.

eng

IM

MEDLINE

0193-1849

Print

NLM

E1195-205

pubmed-meshheading:15644454-Acetyl-CoA Carboxylase, pubmed-meshheading:15644454-Animals, pubmed-meshheading:15644454-Azo Compounds, pubmed-meshheading:15644454-CCAAT-Enhancer-Binding Proteins, pubmed-meshheading:15644454-Carrier Proteins, pubmed-meshheading:15644454-Chromans, pubmed-meshheading:15644454-DNA-Binding Proteins, pubmed-meshheading:15644454-Fatty Acid Synthetase Complex, pubmed-meshheading:15644454-Fatty Acid-Binding Proteins, pubmed-meshheading:15644454-Fatty Liver, pubmed-meshheading:15644454-Gene Expression, pubmed-meshheading:15644454-Hepatocytes, pubmed-meshheading:15644454-Hypoglycemic Agents, pubmed-meshheading:15644454-Lipid Metabolism, pubmed-meshheading:15644454-Male, pubmed-meshheading:15644454-Membrane Proteins, pubmed-meshheading:15644454-Mice, pubmed-meshheading:15644454-Mice, Inbred C57BL, pubmed-meshheading:15644454-Mice, Obese, pubmed-meshheading:15644454-Microscopy, Confocal, pubmed-meshheading:15644454-PPAR gamma, pubmed-meshheading:15644454-RNA, Messenger, pubmed-meshheading:15644454-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:15644454-Sterol Regulatory Element Binding Protein 1, pubmed-meshheading:15644454-Thiazolidinediones, pubmed-meshheading:15644454-Transcription Factors, pubmed-meshheading:15644454-Triglycerides

PPARgamma2 regulates lipogenesis and lipid accumulation in steatotic hepatocytes.

Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural