A dysregulated Acetyl/SUMO switch of FXR promotes hepatic inflammation in obesity

ABSTRACT: Acetylation of transcriptional regulators is normally dynamically regulated by nutrient status but is often persistently elevated in nutrient-excessive obesity conditions. We investigated the functional consequences of such aberrantly elevated acetylation of the nuclear receptor FXR as a model. Proteomic studies identified K217 as the FXR acetylation site in diet-induced obese mice. In vivo studies utilizing acetylation-mimic and -defective K217 mutants and gene expression profiling revealed that FXR acetylation increased proinflammatory gene expression, macrophage infiltration, and liver cytokine and triglyceride levels, impaired insulin signaling, and increased glucose intolerance. Mechanistically, acetylation of FXR blocked its interaction with the SUMO ligase PIASy and inhibited SUMO2

ORGANISM(S): Mus musculus

SUBMITTER: Jongsook Kemper 

PROVIDER: E-GEOD-62414 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress