PGC-1? and ChREBP partner to cooperatively regulate hepatic lipogenesis in a glucose concentration-dependent manner.

ABSTRACT: Peroxisome proliferator-activated receptor? coactivators (PGC-1? and PGC-1?) play important roles in the transcriptional regulation of intermediary metabolism. To evaluate the effects of overexpressing PGC-1? or PGC-1? at physiologic levels in liver, we generated transgenic mice with inducible overexpression of PGC-1? or PGC-1?. Gene expression array profiling revealed that whereas both PGC-1 family proteins induced mitochondrial oxidative enzymes, the expression of several genes involved in converting glucose to fatty acid was induced by PGC-1?, but not PGC-1?. The increased expression of enzymes involved in carbohydrate utilization and de novo lipogenesis by PGC-1? required carbohydrate response element binding protein (ChREBP). The interaction between PGC-1? and ChREBP, as well as PGC-1? occupancy of the liver-type pyruvate kinase promoter, was influenced by glucose concentration and liver-specific PGC-1?(-/-) hepatocytes were refractory to the lipogenic response to high glucose conditions. These data suggest that PGC-1?-mediated coactivation of ChREBP is involved in the lipogenic response to hyperglycemia.

SUBMITTER: Chambers KT 

PROVIDER: S-EPMC3773825 | biostudies-other | 2013

REPOSITORIES: biostudies-other