Document Detail

Retinol binding protein 4 stimulates hepatic sterol regulatory element-binding protein 1 and increases lipogenesis through the peroxisome proliferator-activated receptor-γ coactivator 1β-dependent pathway.
MedLine Citation:
PMID:  23300015     Owner:  NLM     Status:  MEDLINE    
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 in 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 lipogenesis. Treatment with human retinol-bound RBP4 (holo-RBP4) significantly induced intracellular triglyceride (TAG) synthesis in HepG2 cells and this effect is retinol-independent. Furthermore, RBP4 treatment enhanced the levels of 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 up-regulated the expression of transcriptional coactivator peroxisome proliferator-activated receptor-γ coactivator 1β (PGC-1β) at both the messenger RNA (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 cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB) was identified as the target transcription factor involved in the RBP4-mediated up-regulation 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 TAG in C57BL/6J mice, a phenomenon not observed in Ppargc1b knockout mice. Conclusion: These findings reveal a novel mechanism by which RBP4 achieves its effects on hepatic lipid metabolism.
Min Xia; Yan Liu; Honghui Guo; Duan Wang; Yun Wang; Wenhua Ling
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-06-14
Journal Detail:
Title:  Hepatology (Baltimore, Md.)     Volume:  58     ISSN:  1527-3350     ISO Abbreviation:  Hepatology     Publication Date:  2013 Aug 
Date Detail:
Created Date:  2013-07-30     Completed Date:  2014-01-16     Revised Date:  2014-07-10    
Medline Journal Info:
Nlm Unique ID:  8302946     Medline TA:  Hepatology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  564-75     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 American Association for the Study of Liver Diseases.
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MeSH Terms
Cell Line, Tumor
Cyclic AMP Response Element-Binding Protein / metabolism
Hep G2 Cells / drug effects,  metabolism,  pathology
Lipogenesis / drug effects*
Liver / drug effects,  metabolism,  pathology
Mice, Inbred C57BL
Mice, Knockout
Models, Animal
Retinol-Binding Proteins, Plasma / pharmacology*
Signal Transduction / drug effects*
Sterol Regulatory Element Binding Protein 1 / metabolism*
Transcription Factors / deficiency,  genetics,  metabolism*
Up-Regulation / drug effects
Reg. No./Substance:
0/Creb1 protein, mouse; 0/Cyclic AMP Response Element-Binding Protein; 0/Ppargc1a protein, mouse; 0/Rbp4 protein, mouse; 0/Retinol-Binding Proteins, Plasma; 0/Srebf1 protein, mouse; 0/Sterol Regulatory Element Binding Protein 1; 0/Transcription Factors
Comment In:
Hepatology. 2014 Jun;59(6):2422   [PMID:  24115261 ]
Hepatology. 2013 Aug;58(2):477-9   [PMID:  23703940 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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