Dual peroxisome-proliferator-activated-receptor-α/γ activation inhibits SIRT1-PGC1α axis and causes cardiac dysfunction.

ABSTRACT: Dual peroxisome proliferator-activated receptor (PPAR)α/γ agonists that were developed to target hyperlipidemia and hyperglycemia in type 2 diabetes patients, caused cardiac dysfunction or other adverse effects. We studied the mechanisms that underlie the cardiotoxic effects of a dual PPARα/γ agonist, tesaglitazar, in wild type and diabetic (leptin receptor deficient - db/db) mice. Mice treated with tesaglitazar-containing chow or high fat diet developed cardiac dysfunction despite lower plasma triglycerides and glucose levels. Expression of cardiac peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), which promotes mitochondrial biogenesis, had the most profound reduction among various fatty acid metabolism genes. Furthermore, we observed increased acetylation of

SUBMITTER: Kalliora C 

PROVIDER: S-EPMC6777908 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature