The liver transcription factor ChREBP: from glucose-sensing to hepatic steatosis
Event details
| Date | 19.01.2012 |
| Hour | 14:00 |
| Speaker | Dr. Catherine POSTIC- INSERM, U1016, Paris, France; CNRS, UMR8104, Paris, France; Université Paris Descartes, Paris, France |
| Location | |
| Category | Conferences - Seminars |
Over the recent years our team has aimed at identifying new potential targets for the treatment and/or prevention of hyperglycemia, insulin resistance and related metabolic alterations (hepatic steatosis/hyperlipidemia) in gain and/or loss of function mouse models. In particular, we have studied the function and regulation of the glucose-sensitive transcription factor ChREBP in mouse liver. We showed that its inhibition, by decreasing the rate of lipogenesis, improved hepatic steatosis and insulin resistance in obese ob/ob mice. We identified glucose 6-phosphate as the signal metabolite responsible for ChREBP nuclear translocation and activation in response to glucose in liver. We also determined that various post-translational modifications (acetylation, O-glycosylation) govern ChREBP activity in response to glucose and how they relate to the pathophysiology of hepatic steatosis in mice and humans.
Selected publications:
Dentin R, Benhamed F, Hainault I, Fauveau V, Foufelle F, Dyck JR, Girard J, Postic C. Liver-specific inhibition of ChREBP improves hepatic steatosis and insulin resistance in ob/ob mice. Diabetes 55(8):2159-70 (2006).
Denechaud PD, Bossard P, Lobaccaro JM, Millat L, Staels B, Girard J, and Postic, C. ChREBP, but not LXRs, is required for the induction of glucose-regulated genes in liver. J. Clin. Invest. 118(3):956-64(2008).
Bricambert J, Miranda J, Benhamed F, Girard J, Postic C, Dentin R. Salt-inducible kinase 2 links transcriptional coactivator p300 phosphorylation to the prevention of ChREBP-dependent hepatic steatosis in mice. J Clin Invest. 1;120(12):4316-31 (2010).
Guinez C, Filhoulaud G, Rayah-Benhamed F, Dubuquoy C, Dentin R, Moldes M, Burnol AF, Lefebvre T, Girard, J and Postic C. O-GlcNAcylation increases ChREBP protein stability and transcriptional activity in liver. Diabetes 60(5):1399-413 (2011).
Dentin R, Tomas-Cobos L, Foufelle F, Leopold J, Girard J, Postic C, Ferré P. Glucose 6-phosphate, rather than xylulose 5-phosphate, is required for the activation of ChREBP in response to glucose in liver. J Hepatol ahead of print (2011).
Practical information
- General public
- Free