Document Detail

Phosphatidylcholines as regulators of glucose and lipid homeostasis: Promises and potential risks.
MedLine Citation:
PMID:  22139705     Owner:  NLM     Status:  In-Data-Review    
Nuclear hormone receptors regulate diverse metabolic pathways and the orphan nuclear receptor LRH-1 (also known as NR5A2) regulates bile acid biosynthesis. Structural studies have identified phospholipids as potential LRH-1 ligands, but their functional relevance is unclear. Here we show that an unusual phosphatidyl-choline species with two saturated 12 carbon fatty acid acyl side chains (dilauroyl phosphatidylcholine (DLPC)) is an LRH-1 agonist ligand in vitro. DLPC treatment induces bile acid biosynthetic enzymes in mouse liver, increases bile acid levels, and lowers hepatic triglycerides and serum glucose. DLPC treatment also decreases hepatic steatosis and improves glucose homeostasis in two mouse models of insulin resistance. Both the antidiabetic and lipotropic effects are lost in liver-specific Lrh-1 knockouts. These findings identify an LRH-1 dependent phosphatidylcholine signalling pathway that regulates bile acid metabolism and glucose homeostasis.
Simon Hohenester; Ulrich Beuers
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Hepatology (Baltimore, Md.)     Volume:  54     ISSN:  1527-3350     ISO Abbreviation:  Hepatology     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-05     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8302946     Medline TA:  Hepatology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2266-8     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 American Association for the Study of Liver Diseases.
Tytgat Institute for Liver and Intestinal Research Department of Gastroenterology & Hepatology University of Amsterdam Amsterdam, The Netherlands.
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