Hepatic peroxisome proliferator-activated receptor alpha 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 PPARα 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. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Citation

Guolin Li, Chad N Brocker, Cen Xie, Tingting Yan, Audrey Noguchi, Kristopher W Krausz, Rong Xiang, Frank J Gonzalez. Hepatic peroxisome proliferator-activated receptor alpha mediates the major metabolic effects of Wy-14643. Journal of gastroenterology and hepatology. 2018 May;33(5):1138-1145

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PMID: 29141109

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