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Phosphatidylcholines as regulators of glucose and lipid homeostasis: Promises and potential risks
Author(s) -
Hohenester Simon,
Beuers Ulrich
Publication year - 2011
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.24697
Subject(s) - glucose homeostasis , homeostasis , chemistry , medicine , neuroscience , endocrinology , biology , diabetes mellitus , insulin resistance
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.