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

Kari T. Chambers, Zhouji Chen, Ling Lai, Teresa C. Leone, Howard C. Towle, Anastasia Kralli, Peter A. Crawford, Brian N. Finck

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Peroxisome proliferator-activated receptorγ coactivators (PGC-1α and PGC-1β) play important roles in the transcriptional regulation of intermediary metabolism. To evaluate the effects of overexpressing PGC-1α or PGC-1β at physiologic levels in liver, we generated transgenic mice with inducible overexpression of PGC-1α or PGC-1β. 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-1β, but not PGC-1α. The increased expression of enzymes involved in carbohydrate utilization and de novo lipogenesis by PGC-1β required carbohydrate response element binding protein (ChREBP). The interaction between PGC-1β and ChREBP, as well as PGC-1β occupancy of the liver-type pyruvate kinase promoter, was influenced by glucose concentration and liver-specific PGC-1β-/- hepatocytes were refractory to the lipogenic response to high glucose conditions. These data suggest that PGC-1β-mediated coactivation of ChREBP is involved in the lipogenic response to hyperglycemia.

Original languageEnglish (US)
Pages (from-to)194-204
Number of pages11
JournalMolecular Metabolism
Volume2
Issue number3
DOIs
StatePublished - Aug 1 2013

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Keywords

  • ChREBP
  • Hepatic
  • Metabolism
  • PGC-1

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