Carbohydrate responsive element binding protein and lipid... : Current Opinion in Lipidology (original) (raw)

Lipid metabolism: Edited by Jeffrey S. Cohn

aCochin Institute, Department of Endocrinology, Metabolism and Cancer, Paris Descartes University, CNRS (UMR 8104), France

bInserm U567, Paris, France

Correspondence to Catherine Postic, Institut Cochin, Département d'Endocrinologie, Métabolisme et Cancer, Université Paris Descartes, CNRS (UMR 8104), Paris, France Tel: +33 1 53 73 27 07; fax: +33 1 53 73 27 03; e. mail: [email protected]

Abstract

Purpose of review

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.

Recent findings

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.

Summary

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.