A nuclear-receptor-dependent phosphatidylcholine pathway with antidiabetic effects.

Title

A nuclear-receptor-dependent phosphatidylcholine pathway with antidiabetic effects.

Creator

Lee Jae Man; Lee Yoon-Kwang; Mamrosh Jennifer L; Busby Scott A; Griffin Patrick R; Pathak Manish C; Ortlund Eric A; Moore David D

Publisher

Nature

Date

2011
2011-06-23

Description

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 phosphatidylcholine 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. [ABSTRACT FROM AUTHOR]

Subject

BILE acids; HOMEOSTASIS; HYPOGLYCEMIC agents; INSULIN resistance; LABORATORY mice; LECITHIN; TRIGLYCERIDES

Identifier

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

506–510

Issue

7352

Volume

474

Citation

Lee Jae Man; Lee Yoon-Kwang; Mamrosh Jennifer L; Busby Scott A; Griffin Patrick R; Pathak Manish C; Ortlund Eric A; Moore David D, “A nuclear-receptor-dependent phosphatidylcholine pathway with antidiabetic effects.,” NEOMED Bibliography Database, accessed February 28, 2021, https://neomed.omeka.net/items/show/5740.

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