Potential conflict of interest: Nothing to report.
Phosphatidylcholines as regulators of glucose and lipid homeostasis: Promises and potential risks†
Article first published online: 30 NOV 2011
Copyright © 2011 American Association for the Study of Liver Diseases
Volume 54, Issue 6, pages 2266–2268, December 2011
How to Cite
Hohenester, S., Beuers, U. (2011), Phosphatidylcholines as regulators of glucose and lipid homeostasis: Promises and potential risks. Hepatology, 54: 2266–2268. doi: 10.1002/hep.24697
- Issue published online: 30 NOV 2011
- Article first published online: 30 NOV 2011
- Manuscript Accepted: 15 SEP 2011
- Manuscript Revised: 7 SEP 2011
- Manuscript Received: 15 AUG 2011
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.