A MED13-dependent skeletal muscle gene program controls systemic glucose homeostasis and hepatic metabolism.

ABSTRACT: The Mediator complex governs gene expression by linking upstream signaling pathways with the basal transcriptional machinery. However, how individual Mediator subunits may function in different tissues remains to be investigated. Through skeletal muscle-specific deletion of the Mediator subunit MED13 in mice, we discovered a gene regulatory mechanism by which skeletal muscle modulates the response of the liver to a high-fat diet. Skeletal muscle-specific deletion of MED13 in mice conferred resistance to hepatic steatosis by activating a metabolic gene program that enhances muscle glucose uptake and storage as glycogen. The consequent insulin-sensitizing effect within skeletal muscle lowered systemic glucose and insulin levels independently of weight gain and adiposity and prevented hepatic

SUBMITTER: Amoasii L 

PROVIDER: S-EPMC4762428 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature