Transcriptional regulation of the adipocyte fatty acid synthase gene by agouti: Interaction with insulin

Kate J. Claycombe, Yanxin Wang, Brynn H. Jones, Suyeon Kim, William O. Wilkison, Michael B. Zemel, Joseph Chun, Naima Moustaid-Moussa

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Mice carrying dominant mutations at the agouti locus exhibit ectopic expression of agouti gene transcripts, obesity, and type II diabetes through unknown mechanisms. To gain insight into the role of agouti protein in modulating adiposity, we investigated regulation of a key lipogenic gene, fatty acid synthase (FAS) by agouti alone and in combination with insulin. Both agouti and insulin increase FAS activity in 3T3-L1 and in human adipocytes. Agouti and insulin independently and additively increase FAS activity in 3T3-L1 adipocytes. We further investigated the mechanism responsible for the agouti-induced FAS expression in these cells and demonstrated that both insulin (3-fold increase) and agouti (2-fold) increased FAS gene expression at the transcriptional level. Furthermore, insulin and agouti together exerted additive effects (5-fold increase) on FAS gene transcription. Transfection assays of FAS promoter-luciferase fusion gene constructs into 3T3-L1 adipocytes indicated that the agouti response element(s) is (are) located in the -435 to -415 region (-435/-415) of the FAS promoter. Nuclear proteins binding to this novel sequence are adipocyte specific. Thus the agouti response sequences mapped to a region upstream of the insulin-responsive element (which we previously reported to be located at -677-52), consistent with additive effects of these two factors on FAS gene transcription.

Original languageEnglish
Pages (from-to)157-162
Number of pages6
JournalPhysiological Genomics
Volume2000
Issue number3
DOIs
StatePublished - Sep 2000

Keywords

  • Gene transcription
  • Regulatory sequences

Fingerprint

Dive into the research topics of 'Transcriptional regulation of the adipocyte fatty acid synthase gene by agouti: Interaction with insulin'. Together they form a unique fingerprint.

Cite this