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Text
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URL Address
<a href="http://doi.org/10.1038/nature10111" target="_blank" rel="noreferrer noopener">http://doi.org/10.1038/nature10111</a>
Pages
506–510
Issue
7352
Volume
474
Dublin Core
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Title
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A nuclear-receptor-dependent phosphatidylcholine pathway with antidiabetic effects.
Publisher
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Nature
Date
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2011
2011-06-23
Subject
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BILE acids; HOMEOSTASIS; HYPOGLYCEMIC agents; INSULIN resistance; LABORATORY mice; LECITHIN; TRIGLYCERIDES
Creator
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Lee Jae Man; Lee Yoon-Kwang; Mamrosh Jennifer L; Busby Scott A; Griffin Patrick R; Pathak Manish C; Ortlund Eric A; Moore David D
Description
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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]
Identifier
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<a href="http://doi.org/10.1038/nature10111" target="_blank" rel="noreferrer noopener">10.1038/nature10111</a>
Rights
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2011
BILE acids
Busby Scott A
Department of Integrative Medical Sciences
Griffin Patrick R
Homeostasis
HYPOGLYCEMIC agents
Insulin Resistance
LABORATORY mice
LECITHIN
Lee Jae Man
Lee Yoon-Kwang
Mamrosh Jennifer L
Moore David D
Nature
NEOMED College of Medicine
Ortlund Eric A
Pathak Manish C
triglycerides