Statins enhance peroxisome proliferator-activated receptor gamma coactivator-1alpha activity to regulate energy metabolism.

Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte
Wenxian Wang, Chi-Wai Wong

Abstract

Peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) serves as an inducible coactivator for a number of transcription factors to control energy metabolism. Insulin signaling through Akt kinase has been demonstrated to phosphorylate PGC-1alpha at serine 571 and downregulate its activity in the liver. Statins are 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors that reduce cholesterol synthesis in the liver. In this study, we found that statins reduced the active form of Akt and enhanced PGC-1alpha activity. Specifically, statins failed to activate an S571A mutant of PGC-1alpha. The activation of PGC-1alpha by statins selectively enhanced the expression of energy metabolizing enzymes and regulators including peroxisome proliferator-activated receptor alpha, acyl-CoA oxidase, carnitine palmitoyl transferase-1A, and pyruvate dehydrogenase kinase 4. Importantly, a constitutively active form of Akt partially reduced the statin-enhanced gene expression. Our study thus provides a plausible mechanistic explanation for the hypolipidemic effect of statin through elevating the rate of beta-oxidation and mitochondrial Kreb's cycle capacity to enhance fatty acid utilization while reducing the rate of gly...Continue Reading

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Citations

Nov 1, 2011·Antioxidants & Redox Signaling·Jerzy Bełtowski, Anna Jamroz-Wiśniewska
Mar 21, 2017·Biochemical and Biophysical Research Communications·Yintao ChenYingxian Sun
Sep 16, 2017·International Journal of Molecular Sciences·Heidrun KarlicFranz Varga
Jul 30, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Laura TrapaniValentina Pallottini
Mar 10, 2021·The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi·Jin LeeSea Hyub Kae
Feb 9, 2011·Biochemical Pharmacology·Giulia Maria CamerinoRoberto Bottinelli

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