Document Detail


The human fatty acid synthase gene and de novo lipogenesis are coordinately regulated in human adipose tissue.
MedLine Citation:
PMID:  15113941     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Despite its potential importance in obesity and related disorders, little is known about regulation of lipogenesis in human adipose tissue. To investigate this area at the molecular and mechanistic levels, we studied lipogenesis and the regulation of 1 of its core enzymes, fatty acid synthase (FAS), in human adipose tissue in response to hormonal and nutritional manipulation. As a paradigm for lipogenic genes, we cloned the upstream region of the human FAS gene, compared its sequence to that of FAS orthologs from other species, and identified important regulatory elements that lie upstream of the FAS coding region. Lipogenesis, as assessed by glucose incorporation into lipids, was increased by insulin and more so by the combination of insulin and dexamethasone (Dex, a potent glucocorticoid analogue). In parallel, FAS expression, activity, and gene transcription rate were also significantly increased by these treatments. We also showed that linoleic acid, a representative PUFA, attenuated the actions of insulin and Dex on fatty acid and lipid synthesis as well as FAS activity and expression. Using reporter assays, we determined that the regions responsible for hormonal regulation of the FAS gene lie in the proximal portion of the gene's 5'-flanking region, within which we identified an insulin response element similar to the E-box sequence we identified previously in the rat FAS gene. In summary, we demonstrated that lipogenesis occurs in human adipose tissue and can be induced by insulin, further enhanced by glucocorticoids, and suppressed by PUFA in a hormone-dependent manner.
Authors:
Yanxin Wang; Brynn Jones Voy; Sumithra Urs; Suyeon Kim; Morvarid Soltani-Bejnood; Neil Quigley; Young-Ran Heo; Melissa Standridge; Brett Andersen; Madhu Dhar; Rashika Joshi; Patrick Wortman; James W Taylor; Joseph Chun; Michael Leuze; Kate Claycombe; Arnold M Saxton; Naima Moustaid-Moussa
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  The Journal of nutrition     Volume:  134     ISSN:  0022-3166     ISO Abbreviation:  J. Nutr.     Publication Date:  2004 May 
Date Detail:
Created Date:  2004-04-28     Completed Date:  2004-06-10     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0404243     Medline TA:  J Nutr     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1032-8     Citation Subset:  IM    
Affiliation:
Department of Nutrition and Agricultural Experiment Station, University of Tennessee, Knoxville, TN 37996-1920,USA.
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MeSH Terms
Descriptor/Qualifier:
Adipose Tissue / enzymology,  metabolism*
Adult
Base Sequence
Culture Techniques
Dexamethasone / pharmacology
Fatty Acid Synthetase Complex / genetics*
Fatty Acids / biosynthesis
Female
Gene Expression
Gene Expression Regulation*
Glucocorticoids / pharmacology
Glucose / metabolism
Humans
Insulin / pharmacology
Lipids / biosynthesis*
Middle Aged
Molecular Sequence Data
Promoter Regions, Genetic / physiology
Chemical
Reg. No./Substance:
0/Fatty Acids; 0/Glucocorticoids; 0/Lipids; 11061-68-0/Insulin; 50-02-2/Dexamethasone; 50-99-7/Glucose; EC 6.-/Fatty Acid Synthetase Complex

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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