Regulation of adipose cell differentiation. II. Kinetics of induction of the aP2 gene by fatty acids and modulation by dexamethasone.
Fatty acids behave as activators of the aP2 gene expression in committed, lipid-free, non-terminally differentiated Ob1771 cells. Like fatty acids, dexamethasone provokes a dose-dependent accumulation of aP2 mRNA. However, fatty acids and dexamethasone act through different mechanisms to activate the aP2 gene expression since i) fatty acids and dexamethasone act in a synergistic manner; ii) the effect of dexamethasone is rapid and transient (maximal effect after 8 h), whereas that of fatty acids is slower, and maintained as long as the inducer is present and is fully reversible upon fatty acid removal; iii) the induction of the aP2 gene expression by dexamethasone does not require ongoing protein synthesis, while the response to fatty acids is completely prevented by cycloheximide; and iv) the induction of the aP2 gene expression by fatty acids but not by dexamethasone is confined to preadipocyte cell lines. This suggests that the process of activation by fatty acids, rather than the expression of the aP2 gene, is unique to adipose cells. Besides their effects on the aP2 gene, fatty acids activate the expression of the acyl CoA synthetase gene which encodes another protein involved in fatty acid metabolism. Activation of both genes by fatty acids appears not to be mediated by the CCAAT enhancer binding protein, a nuclear factor reported as transactivator of the aP2 promoter activity, since the enhancer binding protein mRNA is not expressed under these conditions.
Amri
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EZ
Centre de Biochimie (CNRS-UMR 134), U.F.R. Sciences, Université de Nice-Sophia Antipolis, France.
Ailhaud
G
G
Grimaldi
P
P
D000273:Adipose Tissue / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins; D002352:Carrier Proteins / Q000235:genetics*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D003066:Coenzyme A Ligases / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D007700:Kinetics; D009363:Neoplasm Proteins; D009687:Nuclear Proteins / Q000235:genetics; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D022762:CCAAT-Enhancer-Binding Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D003907:Dexamethasone; D003066:Coenzyme A Ligases