Biochemical and Biophysical Research Communications
Regulation of lipogenesis via BHLHB2/DEC1 and ChREBP feedback looping
Section snippets
Materials and methods
Animals, isolation of rat primary hepatocytes, and cell culture. The protocols for all animal experiments were approved by the Institutional Animal Care and Use Committee of Gunma University Medical School (code no. 08–025). Rat primary hepatocytes were isolated from 6-week-old male Wister rats by the collagenase perfusion methods [4]. Isolated hepatocytes were suspended with DMEM supplemented with 10% fetal calf serum (FCS), 100 nM insulin, 100 nM dexamethasone (dex), 10 nM triiodothronine (T3),
Glucose activation of Bhlhb2 gene expression
Increases in Bhlhb2 mRNA have been reported for diabetic and insulin-resistant patients, and insulin is known to increase Bhlhb2 expression [5], [8]; however, whether glucose activates Bhlhb2 expression remains unclear. Mouse, rat, and human proximal Bhlhb2 promoters contain the conserved ChoRE, which is composed of one perfect E-box and one imperfect E-box, separated by 5-bp spaces (Fig. 1A). Lpk and Fasn are well known to be glucose-response genes targeted by ChREBP [1].
We therefore used Lpk
Discussion
In this study, we show that the glucose-activated transcription factor, ChREBP, regulates mouse Bhlhb2 gene expression by directly binding to ChoRE in the mouse Bhlhb2 promoter. BHLHB2 competes with ChREBP for binding to ChoRE and suppresses the transactivities of Fasn, Lpk, and Bhlhb2 promoter mediated by ChREBP. These data indicate that BHLHB2 and ChREBP coordinately regulate de novo lipogenesis in the rat liver.
We also show that CHREBP induces Bhlhb2 mRNA expression by binding to ChoRE in
Acknowledgments
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.
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