Hepatic PPARα mediates the major metabolic effects of Wy-14643.

Peroxisome proliferator-activated receptor alpha (PPARα) is a molecular target of various fibrate drugs clinically used to lower serum lipids. However, the tissue-specific functions of PPARα remain to be elucidated. This study aimed to explore the tissue-specific functions of PPARα in response to Wy-14643. A hepatocyte-specific Ppara knockout mouse line was used to explore the impact of hepatic PPARα activity on the systemic response to treatment with the potent PPARα agonist Wy-14643. Wy-14643 mainly activated hepatic PPARα and regulated the expression of PPARα target genes in liver. Hepatic Ppara disruption abolished the triglyceride lowering effects of Wy-14643, prevented agonist-induced hypophagia, and ablated target gene response in the liver. These findings indicate that Wy-14643 treatment mainly activates hepatic PPARα, and the hypolipidemic and hypophagic effects of Wy-14643 are dependent on PPARα activation within hepatocytes. This article is protected by copyright. All rights reserved.

Citation

Guolin Li, Chad N Brocker, Cen Xie, Tingting Yan, Audrey Noguchi, Kristopher W Krausz, Rong Xiang, Frank J Gonzalez. Hepatic PPARα mediates the major metabolic effects of Wy-14643. Journal of gastroenterology and hepatology. 2017 Nov 15

PMID: 29141109

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