Coordinated control of bile acids and lipogenesis through FXR-dependent regulation of fatty acid synthase

• DOI: 10.1194/jlr.m600342-jlr200
• Publication Date: 2006-09-07T01:24:24Z
• Authors: Karen E. Matsukuma; Mary K. Bennett; Jiansheng Huang; Li Wang; Gregorio Gil; Timothy F. Osborne
• Keywords: Farnesoid X receptor; Retinoid X receptor; Chenodeoxycholic acid; Lipogenesis; Chromatin immunoprecipitation; Response element

We discovered a nuclear receptor element in the FAS promoter consisting of an inverted repeat spaced by one nucleotide (IR-1) and located 21 bases downstream direct sequenced 4 nucleotides (DR-4) oxysterol liver X response element. An IR-1 is present promoters several genes bile acid lipid homeostasis binds farnesoid receptor/retinoid (FXR/RXR) heterodimers to mediate acid-dependent transcription. show that FXR/RXRalpha specifically activated approximately 10-fold addition synthetic FXR agonist transient transfection assays. also demonstrate endogenous directly murine hepatic genome using tissue-based chromatin immunoprecipitation procedure. Furthermore, we feeding wild-type mice chow diet supplemented with natural chenodeoxycholic results significant induction mRNA expression. Thus, have identified novel it mediates FXR/bile regulation gene. These findings provide first evidence for lipogenesis acids mechanistic rationale previously unexplained observations regarding control