The Impact of Cardiac Lipotoxicity on Cardiac Function and Mirnas Signature in Obese and Non-Obese Rats with Myocardial Infarction

Abstract

Cardiac lipotoxicity is involved in the cardiac functional consequences associated with obesity. Therefore, the aim of this study was to explore whether changes in the mitochondrial lipid cardiac profle could refect diferences in cardiac function and structure in obese and non-obese rats with myocardial infarction (MI). Whether these changes can also be refected in a specifc plasma miRNA signature as markers of cardiac damage was also evaluated. Rats were fed with either standard (3.5% fat) or high fat diet (35% fat) for 6 weeks before the induction of MI and sacrifced 4 weeks later. MI showed cardiac lipotoxicity independently of the presence of obesity, although obese and non-obese rats did not present the same cardiac lipid profle at mitochondrial level. Several cardiac lipid species in mitochondria, including cardiolipins and triglycerides, were associated with myocardial fbrosis, with mitochondrial triglyceride levels being independently associated with it; this supports that lipotoxicity can afect cardiac function. MI down-regulated plasma levels of miRNA 15b-5p and 194-5p in obese and non-obese animals, which were associated with cardiac function, mitochondrial lipids and myocardial fbrosis, with miRNA 15b-5p levels being independently associated with cardiac fbrosis. This could support that lipotoxicity could afect heart function by modulating plasma miRNAs.