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SUMMARY:The liver transcription factor ChREBP: from glucose-sensing to hep
 atic steatosis
DTSTART:20120119T140000
DTSTAMP:20260916T055822Z
UID:4eaf4135859f35542d7bba0c3544012dc1fd58d3c690c674135d950e
CATEGORIES:Conferences - Seminars
DESCRIPTION:Dr. Catherine POSTIC- INSERM\, U1016\, Paris\, France\; CNRS\,
  UMR8104\, Paris\, France\; Université Paris Descartes\, Paris\, France\n
 Over the recent years our team has aimed at identifying new potential targ
 ets for the treatment and/or prevention of hyperglycemia\, insulin resista
 nce and related metabolic alterations (hepatic steatosis/hyperlipidemia) i
 n gain and/or loss of function mouse models. In particular\, we have studi
 ed the function  and regulation of the glucose-sensitive transcription fac
 tor ChREBP in mouse liver. We showed that its inhibition\, by decreasing t
 he rate of lipogenesis\, improved hepatic steatosis and insulin resistance
  in obese ob/ob mice. We identified glucose 6-phosphate as the signal meta
 bolite responsible for ChREBP nuclear translocation and activation in resp
 onse to glucose in liver. We also determined that various post-translation
 al 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.\n\nSelected publications:\nDentin R\, Benha
 med F\, Hainault I\, Fauveau V\, Foufelle F\, Dyck JR\, Girard J\, Postic 
 C. Liver-specific inhibition of ChREBP improves hepatic steatosis and insu
 lin resistance in ob/ob mice. Diabetes 55(8):2159-70 (2006).\nDenechaud 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-regu
 lated genes in liver. J. Clin. Invest. 118(3):956-64(2008).\nBricambert J\
 , Miranda J\, Benhamed F\, Girard J\, Postic C\, Dentin R. Salt-inducible 
 kinase 2 links transcriptional coactivator p300 phosphorylation to the pre
 vention of ChREBP-dependent hepatic steatosis in mice. J Clin Invest. 1\;1
 20(12):4316-31 (2010).\nGuinez C\, Filhoulaud G\, Rayah-Benhamed F\, Dubuq
 uoy C\, Dentin R\, Moldes M\, Burnol AF\, Lefebvre T\, Girard\, J and Post
 ic C. O-GlcNAcylation increases ChREBP protein stability and transcription
 al activity in liver. Diabetes 60(5):1399-413 (2011).\nDentin R\, Tomas-Co
 bos L\, Foufelle F\, Leopold J\, Girard J\, Postic C\, Ferré P. Glucose 6
 -phosphate\, rather than xylulose 5-phosphate\, is required for the activa
 tion of ChREBP in response to glucose in liver. J Hepatol  ahead of print 
 (2011).
LOCATION:AI 1153 https://plan.epfl.ch/?room==AI%201153
STATUS:CONFIRMED
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