Phosphatidylcholine and endogenous PPARalpha ligand activity
Kofi
inflammation and fatigue. Well, it may be boosting natural PPARalpha
ligands in the body - which is why I've been looking at PPARalpha/OCTN2
now for several years. I think this helps explain why Perque liquid
choline helps with my colitis - which is pretty much one of your few
options if you're allergic to soybeans like I am.
Cell. 2009 Aug 7;138(3):476-88. Epub 2009 Jul 30
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Identification of a physiologically relevant endogenous ligand for
PPARalpha in liver.
Chakravarthy MV, Lodhi IJ, Yin L, Malapaka RR, Xu HE, Turk J,
Semenkovich CF.
Endocrinology, Metabolism, and Lipid Research, Department of Medicine,
Washington University School of Medicine, Campus Box 8127, 660 South
Euclid Avenue, St. Louis, MO 63110, USA.
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.
Publication Types:
* Research Support, N.I.H., Extramural
* Research Support, Non-U.S. Gov't
PMID: 19646743