Roles of Increase Fatty Acid Utilization in the Pathological Pathway of Heart Failure in Diabetes

Abstract

This paper reviews the molecular mechanism that led diabetic patients to its major complication heart failure. While AGEs, RAAS, impaired Ca2+ handling, and ER stress also contribute to the progress of diabetic cardiomyopathy, this review emphasizes on the effect of increasing fatty acid (FA) uptake and utilization since it interconnects with other crucial causes of diabetic cardiomyopathy such as lipotoxicity, mitochondrial dysfunction, and myocardial apoptosis. The review started with the root of increasing myocardial FA metabolism, which is the overactivation of a transcription factor called peroxisome proliferator-activated receptor (PPAR). Then, the paper detailedly reviews the molecular mechanism of how increasing FA oxidation and impaired glucose oxidation leads to lipid accumulation, apoptosis, and cardiac inefficiency, which ultimately causes contractile dysfunction, left ventricular hypertrophy, and heart failure.