Loss of Lipoprotein Lipase-derived Fatty Acids Leads to Increased Cardiac Glucose Metabolism and Heart Dysfunction

摘要: Long-chain fatty acids (FAs) are the predominant energy substrate utilized by adult heart. The heart can utilize unesterified FA bound to albumin or obtained from lipolysis of lipoprotein-bound triglyceride (TG). We used heart-specific lipoprotein lipase knock-out mice (hLpL0) test whether these two sources interchangeable and necessary for optimal function. Hearts unable obtain TG were able compensate increasing glucose uptake, glycolysis, oxidation. HLpL0 hearts had decreased expression pyruvate dehydrogenase kinase 4 increased cardiomyocyte transporter 4. Conversely, oxidation rates reduced in isolated perfused hLpL0 hearts. Following abdominal aortic constriction levels genes regulating metabolism acutely up-regulated control mice, yet all died within 48 h constriction. Older developed cardiac dysfunction characterized fractional shortening interstitial perivascular fibrosis. several associated with transforming growth factor-β signaling. Thus, long term reduction uptake is impaired function despite a compensatory increase utilization.