TY - JOUR
T1 - Regulation of lipogenesis via BHLHB2/DEC1 and ChREBP feedback looping
AU - Iizuka, Katsumi
AU - Horikawa, Yukio
N1 - Funding Information:
This work was supported by a Grant in Aid for Scientific Research from the Japan Society for the Promotion of Science (K. Iizuka), the ONO Medical Research Foundation (K. Iizuka) and in part, by a New Energy and Industrial Technology Development Organization grant to Y. Horikawa.
PY - 2008/9/12
Y1 - 2008/9/12
N2 - BHLHB2/DEC1 is a transcription factor implicated in cell proliferation, apoptosis, and metabolism, and is also known to play an important role in the regulation of the mammalian circadian rhythm. However, its precise role in metabolism remains unclear. We investigated the link between BHLHB2 and ChREBP, a glucose-activated transcription factor involved in the regulation of lipogenesis. Glucose stimulation and overexpression of dominant active ChREBP induced Bhlhb2 mRNA expression in rat hepatocytes. Deletion studies showed that ChoRE (-160 to -143 bp) in the mouse Bhlhb2 promoter region is functional in vivo. Overexpression of BHLHB2 inhibited glucose and ChREBP-mediated induction of rat Fasn and liver pyruvate kinase (Lpk) mRNA. ChIP assay demonstrated that BHLHB2 bound to ChoRE in the Fasn, Lpk, and Bhlhb2 promoter regions in vivo. In conclusion, BHLHB2 and ChREBP constitute a novel feedback loop involved in the regulation of lipogenesis.
AB - BHLHB2/DEC1 is a transcription factor implicated in cell proliferation, apoptosis, and metabolism, and is also known to play an important role in the regulation of the mammalian circadian rhythm. However, its precise role in metabolism remains unclear. We investigated the link between BHLHB2 and ChREBP, a glucose-activated transcription factor involved in the regulation of lipogenesis. Glucose stimulation and overexpression of dominant active ChREBP induced Bhlhb2 mRNA expression in rat hepatocytes. Deletion studies showed that ChoRE (-160 to -143 bp) in the mouse Bhlhb2 promoter region is functional in vivo. Overexpression of BHLHB2 inhibited glucose and ChREBP-mediated induction of rat Fasn and liver pyruvate kinase (Lpk) mRNA. ChIP assay demonstrated that BHLHB2 bound to ChoRE in the Fasn, Lpk, and Bhlhb2 promoter regions in vivo. In conclusion, BHLHB2 and ChREBP constitute a novel feedback loop involved in the regulation of lipogenesis.
UR - http://www.scopus.com/inward/record.url?scp=47749120570&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=47749120570&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2008.06.101
DO - 10.1016/j.bbrc.2008.06.101
M3 - Article
C2 - 18602890
AN - SCOPUS:47749120570
SN - 0006-291X
VL - 374
SP - 95
EP - 100
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -