Insulin-stimulated fatty acid synthase gene expression does not require increased sterol response element binding protein 1 transcription in primary adipocytes.
Sterol response element binding protein 1c (SREBP-1c) is a transcription factor that has been implicated in the regulation of expression of key lipogenic genes in hepatocytes, including fatty acid synthase (FAS) and glucokinase. In hepatocytes, insulin stimulates a rapid increase in transcription of SREBP-1c and the appearance of the SREBP-1c protein in the nucleus. SREBP-1 has also been proposed to play an important role in the induction of expression of lipogenic enzymes in adipose tissue in vivo in response to nutritional status. In this paper we have investigated the regulation of the SREBP-1 and FAS genes in adipocytes and find that while an overexpressed constitutively active SREBP-1 mutant is capable of substantially stimulating the FAS promoter, insulin appears to stimulate FAS gene expression in primary adipocytes in the absence of any apparent effect on SREBP-1 transcription. Taken together, our data suggest that insulin does not stimulate FAS gene expression through increasing SREBP-1c transcription in adipose cells.
Palmer
D Gail
DG
Department of Biochemistry, University Walk, Bristol, BS8 1TD, United Kingdom.
Rutter
Guy A
GA
Tavaré
Jeremy M
JM
D017667:Adipocytes / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D002999:Clone Cells; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D064429:Fatty Acid Synthases / Q000096:biosynthesis / Q000235:genetics*; D017930:Genes, Reporter; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D051379:Mice; D009154:Mutation; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D015533:Transcriptional Activation
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D007328:Insulin; D012333:RNA, Messenger; C497388:Srebf1 protein, mouse; C497389:Srebf1 protein, rat; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D064429:Fatty Acid Synthases