Carbohydrate responsive element binding protein and lipid homeostasis.
OBJECTIVE
The liver is responsible for the conversion of excess dietary carbohydrates into fatty acids, through de-novo lipogenesis. A clear understanding of the control of lipogenesis is crucial since excess fatty acids leads to hepatic steatosis and associated metabolic diseases. The transcription factor sterol regulatory element binding protein 1c and the nuclear receptor liver X receptor are implicated in the insulin-mediated induction of lipogenic genes. Recently, the transcription factor carbohydrate responsive element binding protein has emerged as the hepatic glucose sensor required for the induction of lipogenic genes in response to glucose.


RESULTS
We have recently demonstrated that the liver-specific inhibition of carbohydrate responsive element binding protein decreases the rate of lipogenesis and improves hepatic steatosis and insulin resistance in obese ob/ob mice. These results suggest that carbohydrate responsive element binding protein is a potential therapeutic target, and an accurate knowledge of the mechanisms involved in regulating its expression or activation is needed for the development of pharmacological approaches for the treatment of metabolic diseases. Recent studies report that carbohydrate responsive element binding protein is regulated at the transcriptional level by glucose and by liver X receptor but that posttranslational modifications are needed for carbohydrate responsive element binding protein to become active.


CONCLUSIONS
Here we review some of the studies that provided a better understanding of the role and regulation of the newly identified transcription factor carbohydrate responsive element binding protein in lipid homeostasis.
Denechaud
Pierre-Damien
PD
Cochin Institute, Department of Endocrinology, Metabolism and Cancer, Paris Descartes University, CNRS (UMR 8104), Paris, France.
Girard
Jean
J
Postic
Catherine
C
D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D050356:Lipid Metabolism / Q000502:physiology*; D011499:Protein Processing, Post-Translational
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C442825:Mlxipl protein, rat