Thyroid hormone receptor {beta} (TR{beta}) and liver X receptor (LXR) regulate carbohydrate response element binding protein (ChREBP) expression in a tissue selective manner. - Archive ouverte HAL Access content directly
Journal Articles Journal of Biological Chemistry Year : 2010

Thyroid hormone receptor {beta} (TR{beta}) and liver X receptor (LXR) regulate carbohydrate response element binding protein (ChREBP) expression in a tissue selective manner.

(1) , (1) , (1) , (2) , (3) , (1) , (1)
1
2
3

Abstract

Thyroid hormone- (TR) and Liver X- (LXR)receptors are transcription factors involved in lipogenesis. Both receptors recognize the same consensus DNA response element in vitro. It was previously shown that their signalling pathways interact in the control of cholesterol elimination in the liver. In the present study ChREBP, a major transcription factor controlling the activation of glucose-induced lipogenesis in liver, is characterized as a direct target of thyroid hormones(TH) in liver and white adipose tissue(WAT), the two main lipogenic tissues in mice. Using genetic and molecular approaches ChREBP is shown to be specifically regulated by TRbeta, but not by TRalpha in vivo even in WAT where both TR isoforms are expressed. However this isotype specificity is not found in vitro. This TRbeta specific regulation correlates with the loss of TH-induced lipogenesis in TRbeta-/- mice. Fasting/refeeding experiments show that TRbeta is not required for the activation of ChREBP expression particularly marked in WAT following refeeding. However TH can stimulate ChREBP expression in WAT even under fasting conditions suggesting completely independent pathways. Since ChREBP has been described as an LXR target, the interaction of LXR and TRbeta in ChREBP regulation was assayed both in vitro and in vivo. Each receptor recognizes a different response element on the ChREBP promoter, located only eight base pairs apart.There is a crosstalk between LXR and TRbeta signalling on the ChREBP promoter in liver but not in WAT where LXR does not regulate ChREBP expression. The molecular basis for this crosstalk has been determined in in vitro systems.
Fichier principal
Vignette du fichier
JBC-2010-ChREBP.pdf (465.7 Ko) Télécharger le fichier
Origin : Files produced by the author(s)
Loading...

Dates and versions

ensl-00504212 , version 1 (20-07-2010)

Licence

Copyright

Identifiers

Cite

Karine Gauthier, Billon Cyrielle, Marie Bissler, Michel Beylot, Jean-Marc A. Lobaccaro, et al.. Thyroid hormone receptor {beta} (TR{beta}) and liver X receptor (LXR) regulate carbohydrate response element binding protein (ChREBP) expression in a tissue selective manner.. Journal of Biological Chemistry, 2010, 285 (epub ahead of print), epub ahead of print. ⟨10.1074/jbc.M110.146241⟩. ⟨ensl-00504212⟩
265 View
523 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More