Role of ChREBP in hepatic steatosis and insulin resistance.
Non-alcoholic fatty liver disease is tightly associated with insulin resistance, type 2 diabetes and obesity, but the molecular links between hepatic fat accumulation and insulin resistance are not fully identified. Excessive accumulation of triglycerides (TG) is one the main characteristics of non-alcoholic fatty liver disease and fatty acids utilized for the synthesis of TG in liver are available from the plasma non-esterified fatty acid pool but also from fatty acids newly synthesized through hepatic de novo lipogenesis. Recently, the transcription factor ChREBP (carbohydrate responsive element binding protein) has emerged as a central determinant of lipid synthesis in liver through its transcriptional control of key genes of the lipogenic pathway, including fatty acid synthase and acetyl CoA carboxylase. In this mini-review, we will focus on the importance of ChREBP in the physiopathology of hepatic steatosis and insulin resistance by discussing the physiological and metabolic consequences of ChREBP knockdown in liver of ob/ob mice.
Denechaud
Pierre-Damien
PD
Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Département d'Endocrinologie, Métabolisme et Cancer, 24 Rue du Faubourg Saint Jacques, Paris, France.
Dentin
Renaud
R
Girard
Jean
J
Postic
Catherine
C
D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D005234:Fatty Liver / Q000503:physiopathology*; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C506001:Mlxipl protein, mouse; D009687:Nuclear Proteins; D014157:Transcription Factors