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Hepatic peroxisome proliferator‐activated receptor alpha mediates the major metabolic effects of Wy‐14643
Author(s) -
Li Guolin,
Brocker Chad N,
Xie Cen,
Yan Tingting,
Noguchi Audrey,
Krausz Kristopher W,
Xiang Rong,
Gonzalez Frank J
Publication year - 2018
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.14046
Subject(s) - fibrate , medicine , endocrinology , agonist , peroxisome proliferator activated receptor , receptor , clofibric acid , hepatocyte , biology , peroxisome , in vitro , biochemistry , cholesterol
Background and Aim 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. Methods 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. Results 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. Conclusions 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.