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Article: Nutritional and insulin regulation of fatty acid synthetase and leptin gene expression through ADD1/SREBP1

TitleNutritional and insulin regulation of fatty acid synthetase and leptin gene expression through ADD1/SREBP1
Authors
KeywordsADD1/SREBP1
Fatty acid synthetase
Insulin
Leptin
Nutritional changes
Issue Date1998
PublisherAmerican Society for Clinical Investigation. The Journal's web site is located at http://www.jci.org
Citation
Journal Of Clinical Investigation, 1998, v. 101 n. 1, p. 1-9 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/42613
ISSN
2015 Impact Factor: 12.575
2015 SCImago Journal Rankings: 8.764
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorKim, JBen_HK
dc.contributor.authorSarraf, Pen_HK
dc.contributor.authorWright, Men_HK
dc.contributor.authorYao, KMen_HK
dc.contributor.authorMueller, Een_HK
dc.contributor.authorSolanes, Gen_HK
dc.contributor.authorLowell, BBen_HK
dc.contributor.authorSpiegelman, BMen_HK
dc.date.accessioned2007-03-23T04:27:50Z-
dc.date.available2007-03-23T04:27:50Z-
dc.date.issued1998en_HK
dc.identifier.citationJournal Of Clinical Investigation, 1998, v. 101 n. 1, p. 1-9en_HK
dc.identifier.issn0021-9738en_HK
dc.identifier.urihttp://hdl.handle.net/10722/42613-
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.en_HK
dc.format.extent504832 bytes-
dc.format.extent25088 bytes-
dc.format.mimetypeapplication/pdf-
dc.format.mimetypeapplication/msword-
dc.languageengen_HK
dc.publisherAmerican Society for Clinical Investigation. The Journal's web site is located at http://www.jci.orgen_HK
dc.relation.ispartofJournal of Clinical Investigationen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectADD1/SREBP1en_HK
dc.subjectFatty acid synthetaseen_HK
dc.subjectInsulinen_HK
dc.subjectLeptinen_HK
dc.subjectNutritional changesen_HK
dc.subject.meshCcaat-enhancer-binding proteinsen_HK
dc.subject.meshDna-binding proteins - genetics - metabolismen_HK
dc.subject.meshHelix-loop-helix motifsen_HK
dc.subject.meshProteins - genetics - metabolismen_HK
dc.subject.meshTranscription factorsen_HK
dc.titleNutritional and insulin regulation of fatty acid synthetase and leptin gene expression through ADD1/SREBP1en_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0021-9738&volume=101&issue=1&spage=1&epage=9&date=1998&atitle=Nutritional+and+insulin+regulation+of+fatty+acid+synthetase+and+leptin+gene+expression+through+ADD1/SREBP1en_HK
dc.identifier.emailYao, KM:kmyao@hku.hken_HK
dc.identifier.authorityYao, KM=rp00344en_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.pmid9421459en_HK
dc.identifier.pmcidPMC508533-
dc.identifier.scopuseid_2-s2.0-0031963963en_HK
dc.identifier.hkuros36594-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0031963963&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume101en_HK
dc.identifier.issue1en_HK
dc.identifier.spage1en_HK
dc.identifier.epage9en_HK
dc.identifier.isiWOS:000071395300001-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridKim, JB=15762514200en_HK
dc.identifier.scopusauthoridSarraf, P=6701739452en_HK
dc.identifier.scopusauthoridWright, M=36822953400en_HK
dc.identifier.scopusauthoridYao, KM=7403234578en_HK
dc.identifier.scopusauthoridMueller, E=7201904339en_HK
dc.identifier.scopusauthoridSolanes, G=6602450868en_HK
dc.identifier.scopusauthoridLowell, BB=7007082784en_HK
dc.identifier.scopusauthoridSpiegelman, BM=7103405130en_HK

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