Related Experiment Video
Updated: Jun 21, 2026

Induction of an Inflammatory Response in Primary Hepatocyte Cultures from Mice
Published on: March 10, 2017
Identification of a physiologically relevant endogenous ligand for PPARalpha in liver
Manu V Chakravarthy1, Irfan J Lodhi, Li Yin
1Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University School of Medicine, Campus Box 8127, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Abstract:
The nuclear receptor PPARalpha is activated by drugs to treat human disorders of lipid metabolism. Its endogenous ligand is unknown. PPARalpha-dependent gene expression is impaired with inactivation of fatty acid synthase (FAS), suggesting that FAS is involved in generation of a PPARalpha ligand. Here we demonstrate the FAS-dependent presence of a phospholipid bound to PPARalpha isolated from mouse liver. Binding was increased under conditions that induce FAS activity and displaced by systemic injection of a PPARalpha agonist. Mass spectrometry identified the species as 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Knockdown of Cept1, required for phosphatidylcholine synthesis, suppressed PPARalpha-dependent gene expression. Interaction of 16:0/18:1-GPC with the PPARalpha ligand-binding domain and coactivator peptide motifs was comparable to PPARalpha agonists, but interactions with PPARdelta were weak and none were detected with PPARgamma. Portal vein infusion of 16:0/18:1-GPC induced PPARalpha-dependent gene expression and decreased hepatic steatosis. These data suggest that 16:0/18:1-GPC is a physiologically relevant endogenous PPARalpha ligand.
Related Concept Videos
Transducer Mechanism: Nuclear Receptors
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
Cell Specific Gene Expression
GPCRs Regulate Adenylyl Cylase Activity
Two...
Internal Receptors
Signal Transduction: Overview
Typically, signal transduction involves three...
Liver Regeneration
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are large...