title: Regulation of SREBP-1 expression and transcriptional action on HKII and FAS genes during fasting and refeeding in rat tissues.
abstract: The sterol regulatory element binding protein 1 (SREBP-1) is regarded as a major factor involved in the nutritional regulation of lipogenesis. The aim of the present work was to demonstrate its involvement in the response of key genes of glucose and lipid metabolism in liver, adipose tissue, and skeletal muscle during fasting and refeeding. The regulation of hexokinase-2 (HKII) was investigated as a marker of the glucose metabolic pathway and that of FAS was investigated as a marker of the lipogenic pathway. The in vivo association of SREBP-1 with the promoter regions of these genes was determined in the different tissues using chromatin immunoprecipitation assays. Fasting decreased, and refeeding restored, FAS and HKII mRNA and protein levels in each tissue. The concomitant measurement of SREBP-1a and SREBP-1c mRNA levels, of mature SREBP-1 protein abundance in nuclear extracts, and of SREBP-1 interaction with target promoters led to the conclusion that SREBP-1 plays a major role in the response of FAS and HKII genes to nutritional regulation in rodents. These data elucidate the important role of SREBP-1 not only in the regulation of lipid metabolism but also of glucose metabolism and energy homeostasis.
authors.affiliation: Unité Mixte de Recherche Institut National de la Santé et de la Recherche Médicale-U449/Institut National de la Recherche Agronomique-U1235, Institut, Lyon, France.
authors.forename: Yvan
authors.initials: Y
authors.lastname: Gosmain
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dif
authors.forename: Vanessa
authors.initials: V
authors.lastname: Berbe
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Loizon
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rieusset
authors.forename: Hubert
authors.initials: H
authors.lastname: Vidal
authors.forename: Etienne
authors.initials: E
authors.lastname: Lefai
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000821:Animal Feed; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005215:Fasting / Q000502:physiology*; D005786:Gene Expression Regulation; D006593:Hexokinase / Q000235:genetics*; D008099:Liver / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics*; D019014:fas Receptor / Q000235:genetics*
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; C497389:Srebf1 protein, rat; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D019014:fas Receptor; D006593:Hexokinase