The molecular mechanism of thyroid hormone (TH) effects to fatty acid metabolism 
in liver is yet to be clear. The carbohydrate response element-binding protein 
(ChREBP) as well as sterol response element-binding protein (SREBP)-1c plays a 
pivotal role in hepatic lipogenesis. Both SREBP-1c and ChREBP are target genes 
of liver X receptors (LXRs). Because LXRs and TH receptors (TRs) cross talk 
mutually in many aspects of transcription, we examined whether TRs regulate the 
mouse ChREBP gene expression. In the current study, we demonstrated that TH 
up-regulated mouse ChREBP mRNA and protein expression in liver. Run-on and 
luciferase assays showed that TH and TR-beta1 positively regulated the ChREBP 
gene transcription. The mouse ChREBP gene promoter contains two direct repeat-4 
sites (LXRE1 and LXRE2) and EMSAs demonstrated that LXR-alpha and TR-beta1 
prefer to bind LXRE1 and LXRE2, respectively. The direct repeat-4 deletion and 
LXRE2 mutants of the promoter deteriorate the positive regulation by TR-beta1, 
indicating that LXRE2 is functionally important for the regulation. We also 
showed that human ChREBP gene expression and promoter activities were 
up-regulated by TH. These data suggest that ChREBP mRNA expression is positively 
regulated by TR-beta1 and TH at the transcriptional level in mammals. This novel 
observation indicates that TH fine-tunes hepatic lipogenesis via regulating 
SREBP-1c and ChREBP gene expression reciprocally.