Abstract 16294: Adipose Tissue Lipolysis Determines the Cardiac Phenotype During Exercise
We have recently shown that exercise-induced cardiac hypertrophy is regulated in a sex-specific manner. In accordance with increased exercise-mediated hypertrophic responses, female mice showed increased lipolytic activity in adipose tissue and corresponding changes in cardiac metabolism during training. The aim of the present study was to assess whether cardiac hypertrophic responses during exercise, associated with the change of cardiac energy substrate availability/utilization, are determined by the rate of exercise-induced and adipose tissue triglyceride lipase (ATGL)-dependent lipolysis in adipose tissue. Four-weeks old female adipose tissue specific ATGL-deficient (atATGL-KO) and wt littermate mice were challenged with active treadmill running for 1.5h/day (0.25m/s) over 4 weeks. Sedentary mice served as controls. Cardiac and metabolic phenotyping was performed including echocardiography, small-animal PET, and peri-exercise indirect calorimetry. atATGL-KO mice exhibited reduced cardiac hypertrophic responses to exercise, when compared to wt mice, measured by echocardiography (percent increase in left ventricular mass (LVM): atATGL-KO: 14.05±0.26%, wt: 27.73±1.05%; p<0.05). Metabolic analysis of the mice indicated, that exercise-induced lipolytic activity, measured in adipose tissue, was significantly reduced in atATGL-KO mice, when compared to wt controls. In addition, whereas FFA plasma levels measured in wt mice upon training were significantly elevated, plasma FFA levels in atATGL-KO mice remained unchanged. Accordingly, the respiratory quotient measured during exercise was significantly higher in atATGL-KO mice, when compared to wt controls, which is indicative of attenuated utilization of FFA by atATGL-deficient mice. In parallel, myocardial FFA (18F-Fluoro-Thia-Palmitate) uptake of trained atATGL-KO mice was significantly lower when compared to wt animals, analyzed by small-animal PET (injected dose (ID)/LVM [%ID/g], atATGL-KO: 6.93±0.7, wt: 23.10±4.32; p<0.05). Collectively, our data provide the first evidence that ATGL, as a key regulator of lipolysis in adipose tissue, determines exercise-induced cardiac hypertrophy by controlling cardiac substrate availability and utilization.
- © 2012 by American Heart Association, Inc.