Abstract 84: Expression of the Transcription Factors PPAR Alpha and Gamma, and Their Target Genes in the Heart of Obese Mice
The Peroxisome-Proliferator Activated Receptors (PPARs) have been identified as key regulators of energy metabolism by sensing fatty acid availability and activating the transcription of enzymes involved in fatty acid and glucose metabolism. In the heart, PPARs have been proven to participate in the development of diseases, such as cardiac hypertrophy and diabetic cardiomyopathy, conditions that have been associated to obesity. Furthermore, the use of PPARs activator drugs is frequent for the treatment of obesity-dependent diseases, such as hypoglycemiant (fibrates) and anti-diabetic (thiazolidinediones) drugs. Therefore, the objective of this project was to characterize the expression of PPARs and some of their target genes involved in fatty acid and glucose metabolism in the heart of obese mice. Mice (C57BL/6) were fed with either a standard chow diet (control group) or a high fat diet (obese group) for three months. Hearts were weighed prior to quantifying protein expression of two PPARs (alpha and gamma), and both mRNA and protein expression of three enzymes (phosphofructokinase (PFK), glycerol-3-phosphate dehydrogenase (GPD1) and glycerol-3-phosphate acyltransferase (GPAT)). Protein levels were measured by western blot, while mRNA levels were quantified by real-time PCR. The obese group presented 41% increase in body weight compared with control mice. However, no change was observed in obese hearts weight compared with control group, meaning that hypertrophy had not been developed yet. The expression of PPAR-alpha was increased 42% in obese mice compared with the control group, suggesting a possible activation of the fatty acid oxidation pathway. PPAR-gamma together with GPD1 and GPAT showed no differences at any level; however, PFK presented 90% increase in mRNA level and 54% increase in protein level in obese mice. Interestingly, decrease in PFK has been reported in any altered PPAR-alpha condition, contrary to our results. These results suggest that there is a dysregulation of the heart’s energetic pathways mediated by PPARs in earlier stages of obesity.
Author Disclosures: A. Ruiz-Velasco: None. A. Rios: None. B. Escalante: None.
- © 2015 by American Heart Association, Inc.