Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/8306
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dc.contributor.authorKim, Jae Bumcat
dc.contributor.authorSarraf, Pashacat
dc.contributor.authorWright, Margaretcat
dc.contributor.authorYao, Kwok M.cat
dc.contributor.authorMueller, Elisabettacat
dc.contributor.authorSolanes Garcia, Gemmacat
dc.contributor.authorLowell, Bradford B.cat
dc.contributor.authorSpiegelman, Bruce M.cat
dc.date.accessioned2009-05-15T08:26:17Z-
dc.date.available2009-05-15T08:26:17Z-
dc.date.issued1998cat
dc.identifier.issn0021-9738cat
dc.identifier.urihttp://hdl.handle.net/2445/8306-
dc.description.abstractThe ability to regulate specific genes of energy metabolism in response to fasting and feeding is an important adaptation allowing survival of intermittent food supplies. However, little is known about transcription factors involved in such responses in higher organisms. We show here that gene expression in adipose tissue for adipocyte determination differentiation dependent factor (ADD) 1/sterol regulatory element binding protein (SREBP) 1, a basic-helix-loop-helix protein that has a dual DNA-binding specificity, is reduced dramatically upon fasting and elevated upon refeeding; this parallels closely the regulation of two adipose cell genes that are crucial in energy homeostasis, fatty acid synthetase (FAS) and leptin. This elevation of ADD1/SREBP1, leptin, and FAS that is induced by feeding in vivo is mimicked by exposure of cultured adipocytes to insulin, the classic hormone of the fed state. We also show that the promoters for both leptin and FAS are transactivated by ADD1/SREBP1. A mutation in the basic domain of ADD1/SREBP1 that allows E-box binding but destroys sterol regulatory element-1 binding prevents leptin gene transactivation but has no effect on the increase in FAS promoter function. Molecular dissection of the FAS promoter shows that most if not all of this action of ADD1/SREBP1 is through an E-box motif at -64 to -59, contained with a sequence identified previously as the major insulin response element of this gene. These results indicate that ADD1/SREBP1 is a key transcription factor linking changes in nutritional status and insulin levels to the expression of certain genes that regulate systemic energy metabolism.eng
dc.format.extent9 p.cat
dc.format.mimetypeapplication/pdfeng
dc.language.isoengeng
dc.publisherAmerican Society for Clinical Investigationcat
dc.relation.isformatofReproducció del document publicat a http://dx.doi.org/10.1172/JCI1411cat
dc.relation.ispartofJournal of Clinical Investigation, 1998, vol. 101, núm. 1, p. 1-9.cat
dc.relation.urihttp://dx.doi.org/10.1172/JCI1411-
dc.rights(c) The American Society for Clinical Investigation, 1998cat
dc.sourceArticles publicats en revistes (Bioquímica i Biomedicina Molecular)-
dc.subject.classificationÀcids grassoscat
dc.subject.classificationLeptinacat
dc.subject.classificationInsulinacat
dc.subject.classificationMetabolisme energèticcat
dc.subject.classificationExpressió gènicacat
dc.subject.otherADD1/SREBP1eng
dc.subject.otherFatty acid synthetaseeng
dc.subject.otherLeptineng
dc.subject.otherNutritional changeseng
dc.subject.otherInsulineng
dc.titleNutritional and insulin regulation of fatty acid synthetase and leptin gene expression through ADD1/SREBP1.eng
dc.typeinfo:eu-repo/semantics/articleeng
dc.typeinfo:eu-repo/semantics/publishedVersion-
dc.identifier.idgrec149420ca
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess-
dc.identifier.pmid9421459-
Appears in Collections:Articles publicats en revistes (Bioquímica i Biomedicina Molecular)

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