Hepatic peroxisome proliferator-activated receptor alpha mediates the major metabolic effects of Wy-14643.

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

SUBMITTER: Li G 

PROVIDER: S-EPMC6334298 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature