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Feedback looping between ChREBP and PPARα in the regulation of lipid metabolism in brown adipose tissues.
MedLine Citation:
PMID:  23831548     Owner:  NLM     Status:  Publisher    
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.
Katsumi Iizuka; Wudelehu Wu; Yukio Horikawa; Masayuki Saito; Jun Takeda
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-7-05
Journal Detail:
Title:  Endocrine journal     Volume:  -     ISSN:  1348-4540     ISO Abbreviation:  Endocr. J.     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-7-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9313485     Medline TA:  Endocr J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Diabetes and Endocrinology, Graduate School of Medicine, Gifu University, Gifu, Japan.
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