ChREBP, a transcriptional regulator of glucose and lipid metabolism.
Dysregulations in hepatic lipid synthesis are often associated with obesity and type 2 diabetes, and therefore a perfect understanding of the regulation of this metabolic pathway appears essential to identify potential therapeutic targets. Recently, the transcription factor ChREBP (carbohydrate-responsive element-binding protein) has emerged as a major mediator of glucose action on lipogenic gene expression and as a key determinant of lipid synthesis in vivo. Indeed, liver-specific inhibition of ChREBP improves hepatic steatosis and insulin resistance in obese ob/ob mice. Since ChREBP cellular localization is a determinant of its functional activity, a better knowledge of the mechanisms involved in regulating its nucleo-cytoplasmic shuttling and/or its post-translational activation is crucial in both physiology and physiopathology. Here, we review some of the studies that have begun to elucidate the regulation and function of this key transcription factor in liver.
Postic
Catherine
C
Département d'Endocrinologie, Métabolisme et Cancer, Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Paris, France. postic@cochin.inserm.fr
Dentin
Renaud
R
Denechaud
Pierre-Damien
PD
Girard
Jean
J
D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000502:physiology*; D008099:Liver / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008820:Mice, Obese; D009687:Nuclear Proteins; D009765:Obesity / Q000150:complications* / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C506001:Mlxipl protein, mouse; D009687:Nuclear Proteins; D014157:Transcription Factors; D005947:Glucose