Carbohydrate response element binding protein (ChREBP) and peroxisome proliferator-activated receptor alpha (PPARα) play an important role in the regulation of lipid metabolism in the liver.
Chrebp and
Ppara mRNA levels are equally abundant in brown adipose tissue and liver. However, their functions in brown adipose tissues are unclear. In this study, we attempted to clarify the role of ChREBP and PPARα using brown adipose HB2 cell lines and tissues from wild type and
Chrebp-/- C57BL/6J mice. In liver and brown adipose tissues,
Chrebpb mRNA levels in the fasting state were much lower than those fed
ad libitum, while
Ppara mRNA levels in the fasting state were much higher than in the fed state. In differentiated brown adipose HB2 cell lines, glucose increased mRNA levels of ChREBP target genes such as
Chrebpb,
Fasn, and
Glut4 in a dose dependent manner, while glucose decreased both
Chrebpa and
Ppara mRNA levels. Accordingly, adenoviral overexpression of ChREBP and a reporter assay demonstrated that ChREBP partially suppressed
Ppara and
Acox mRNA expression. Moreover, in brown adipose tissues from
Chrebp-/- mice,
Chrebpb and
Fasn mRNA levels in the
ad libitum fed state were much lower than those in the fasting state, while
Ppara and
Acox mRNA levels were not. Finally, using Wy14,643, a selective PPARα agonist, and overexpression of PPARα partially suppressed glucose induction of
Chrebpb and
Fasn mRNA in HB2 cells. In conclusion, the feedback loop between ChREBP and PPARα plays an important role in the regulation of lipogenesis in brown adipocytes.
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