Abstract P070: Exercise Prevents Cardiac Diastolic Dysfunction in a Female Model of Over-Nutrition Induced Obesity by Reducing Oxidant Stress and Fibrosis without Lowering Bodyweight

Abstract

Obesity is being classified as a global epidemic by both the WHO and the CDC. Sedentary lifestyle and consumption of a high-fat/high-fructose Western diet (WD) are implicated in this epidemic. Women are particularly vulnerable to obesity related cardiovascular disease. Obese women suffer higher rates of hypertension, insulin resistance and heart failure, especially diastolic heart failure early in their lives. There are no evidence based treatments for diastolic heart failure. We hypothesized that voluntary daily exercise would prevent WD induced diastolic dysfunction by reducing oxidant stress, fibrosis and inflammation. To test this hypothesis, we developed a diastolic heart failure model by subjecting C57BL6/J female mice to a solely WD fed regimen for 16 weeks. We treated a parallel cohort with daily exercise, via voluntary wheel running, for the entire 16 weeks of WD feeding alongside control diet (CD) groups (n=7 for each group). We monitored food consumption, running activity and body weight. After 16 weeks, we assessed diastolic function by cardiac MRI and echocardiography. Detailed myocardial staining and Western blotting were done for cardiac oxidant stress, fibrosis and inflammatory markers. Both imaging modalities revealed diastolic dysfunction with WD feeding that was normalized by voluntary exercise. Mice ran similarly high intensities on both CD (6.5 km/d) and WD (7.1km/d). While WD feeding increased bodyweight, there was no reduction in weight with exercise. Body composition analysis showed WD fed mice treated with voluntary exercise had increases in visceral fat weight similar to sedentary WD fed mice. There was a notable increase in lean body mass with exercise. WD feeding resulted in insulin resistance that was prevented by exercise. Finally, while WD feeding markedly increased oxidant stress and fibrosis in sedentary mice, exercise prevented myocardial oxidant stress and fibrosis. Our work provides seminal evidence that diastolic dysfunction of over-nutrition induced obesity can be prevented by exercise. Surprisingly, our study suggests that the mechanisms behind the amelioration of diastolic dysfunction are predominantly through reductions in oxidant stress and fibrosis without reductions in body weight or visceral fat.