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Retinol binding protein 4 stimulates hepatic SREBP-1 and increases lipogenesis through PGC-1beta-dependent pathway.
MedLine Citation:
PMID:  23300015     Owner:  NLM     Status:  Publisher    
Recent studies have revealed the essential role of retinol binding protein 4 (RBP4) in insulin resistance. However, the impact of RBP4 on aberrant lipogenesis, the common hepatic manifestation under the insulin resistance states, and the underlying mechanism remain elusive. The present study was designed to examine the effect of RBP4 on sterol regulatory element-binding protein (SREBP-1) and hepatic lopogenesis. Treatment with human retinol-bound RBP4 (holo-RBP4) significantly induced intracellular TAG synthesis in HepG2 cells and this effect is retinol independent. Furthermore, RBP4 treatment enhanced the levels of mature mature SREBP-1 and its nuclear translocation, thereby increasing the expression of lipogenic genes, including fatty acid synthase (FAS), acetyl coenzyme A carboxylase-1 (ACC-1) and diacylglycerol O-acyltransferase 2 (DGAT-2). Stimulation of HepG2 cells with RBP4 strongly upregulated the expression of transcriptional coactivator peroxisome proliferator-activated receptor-γ coactivator 1β (PGC-1β) at both mRNA and protein levels. The transcriptional activation of PGC-1β is necessary and sufficient for the transcriptional activation of SREBP-1 in response to RBP4. The cAMP-response element binding protein (CREB) was identified as the target transcription factor involved in the RBP4-mediated upregulation of PGC-1β transcription as a result of phosphorylation on Ser133. Furthermore, in vivo RBP4 infusion induced SREBP-1c activation and consequently accelerated hepatic lipogenesis and plasma triglyceride (TAG) in C57BL/6J mice, a phenomenon was not observed in Ppargc1b knockout mice. Conclusion: Our findings reveal a novel mechanism by which RBP4 achieves its effects on hepatic lipid metabolism. (HEPATOLOGY 2013.).
Min Xia; Yan Liu; Honghui Guo; Duan Wang; Yun Wang; Wenhua Ling
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-8
Journal Detail:
Title:  Hepatology (Baltimore, Md.)     Volume:  -     ISSN:  1527-3350     ISO Abbreviation:  Hepatology     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8302946     Medline TA:  Hepatology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2013 American Association for the Study of Liver Diseases.
Guangdong Provincial Key Laboratory of Food, Nutrition and Health; Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou 510080, Guangdong Province, China.
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