Carbohydrate-response element-binding protein deletion alters substrate utilization producing an energy-deficient liver

Shawn C. Burgess, Katsumi Iizuka, Ho Jeoung Nam, Robert A. Harris, Yoshihiro Kashiwaya, Richard L. Veech, Tatsuya Kitazume, Kosaku Uyeda

研究成果: ジャーナルへの寄稿学術論文査読

49 被引用数 (Scopus)

抄録

Livers from mice lacking the carbohydrate-responsive element-binding protein (ChREBP) were compared with wild type (WT) mice to determine the effect of this transcription factor on hepatic energy metabolism. The pyruvate dehydrogenase complex was considerably more active in ChREBP-/- mice because of diminished pyruvate dehydrogenase kinase activity. Greater pyruvate dehydrogenase complex activity caused a stimulation of lactate and pyruvate oxidation, and it significantly impaired fatty acid oxidation in perfused livers from ChREBP-/- mice. This shift in mitochondrial substrate utilization led to a 3-fold reduction of the free cytosolic [NAD +]/[NADH] ratio, a 1.7-fold increase in the free mitochondrial [NAD+]/[NADH] ratio, and a 2-fold decrease in the free cytosolic [ATP]/[ADP][Pi] ratio in the ChREBP-/- liver compared with control. Hepatic pyruvate carboxylase flux was impaired with ChREBP deletion secondary to decreased fatty acid oxidation, increased pyruvate oxidation, and limited pyruvate availability because of reduced activity of liver pyruvate kinase and malic enzyme, which replenish pyruvate via glycolysis and pyruvate cycling. Overall, the shift from fat utilization to pyruvate and lactate utilization resulted in a decrease in the energy of ATP hydrolysis and a hypo-energetic state in the livers of ChREBP-/- mice.

本文言語英語
ページ(範囲)1670-1678
ページ数9
ジャーナルJournal of Biological Chemistry
283
3
DOI
出版ステータス出版済み - 18-01-2008
外部発表はい

All Science Journal Classification (ASJC) codes

  • 生化学
  • 分子生物学
  • 細胞生物学

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