alexa PPARdelta agonist attenuates alcohol-induced hepatic insulin resistance and improves liver injury and repair.


Journal of Clinical & Experimental Pathology

Author(s): Pang M, de la Monte SM, Longato L, Tong M, He J,

Abstract Share this page

Abstract BACKGROUND/AIMS: Chronic ethanol exposure impairs liver regeneration due to inhibition of insulin signaling and oxidative injury. PPAR agonists function as insulin sensitizers and anti-inflammatory agents. We investigated whether treatment with a PPARdelta agonist could restore hepatic insulin sensitivity, survival signaling, and regenerative responses vis-a-vis chronic ethanol feeding. METHODS: Adult rats were fed isocaloric liquid diets containing 0\% or 37\% ethanol, and administered a PPARdelta agonist by i.p. injection. We used liver tissue to examine histopathology, gene expression, oxidative stress, insulin signaling, and regenerative responses to 2/3 hepatectomy. RESULTS: Chronic ethanol feeding caused insulin resistance, increased oxidative stress, lipid peroxidation, DNA damage, and hepatocellular injury in liver. These effects were associated with reduced insulin receptor binding and affinity, impaired survival signaling through PI3K/Akt/GSK3beta, and reduced expression of insulin responsive genes mediating energy metabolism and tissue remodeling. PPARdelta agonist treatment reduced ethanol-mediated hepatic injury, oxidative stress, lipid peroxidation, and insulin resistance, increased signaling through PI3K/Akt/GSK3beta, and enhanced the regenerative response to partial hepatectomy. CONCLUSIONS: PPARdelta agonist administration may attenuate the severity of chronic ethanol-induced liver injury and ethanol's adverse effects on the hepatic repair by restoring insulin responsiveness, even in the context of continued high-level ethanol consumption.
This article was published in J Hepatol and referenced in Journal of Clinical & Experimental Pathology

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Peer Reviewed Journals
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version