Dataset Information
Hepatic peroxisome proliferator-activated receptor alpha mediates the major metabolic effects of Wy-14643.
Ontology highlight
ABSTRACT: 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.
SUBMITTER: Li G
PROVIDER: S-EPMC6334298 | biostudies-literature | 2018 May
REPOSITORIES: biostudies-literature
Publications
Hepatic peroxisome proliferator-activated receptor alpha mediates the major metabolic effects of Wy-14643.
Journal of gastroenterology and hepatology 20180219 5
<h4>Background and aim</h4>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.<h4>Methods</h4>A hepatocyte-specific Ppara knockout mouse line was used to explore the impact of hepatic PPARα activity on the systemic response to treatment with th ...[more]