Lipoprotein lipase mediated fatty acid delivery and its impact in diabetic cardiomyopathy.
Although cardiovascular disease is the leading cause of diabetes-related death, its etiology is still not understood. The immediate change that occurs in the diabetic heart is altered energy metabolism where in the presence of impaired glucose uptake, glycolysis, and pyruvate oxidation, the heart switches to exclusively using fatty acids (FA) for energy supply. It does this by rapidly amplifying its lipoprotein lipase (LPL-a key enzyme, which hydrolyzes circulating lipoprotein-triglyceride to release FA) activity at the coronary lumen. An abnormally high capillary LPL could provide excess fats to the heart, leading to a number of metabolic, morphological, and mechanical changes, and eventually to cardiac disease. Unlike the initial response, chronic severe diabetes "turns off" LPL, this is also detrimental to cardiac function. In this review, we describe a number of post-translational mechanisms that influence LPL vesicle formation, actin cytoskeleton rearrangement, and transfer of LPL from cardiomyocytes to the vascular lumen to hydrolyze lipoprotein-triglyceride following diabetes. Appreciating the mechanism of how the heart regulates its LPL following diabetes should allow the identification of novel targets for therapeutic intervention, to prevent heart failure. This article is part of a Special Issue entitled Triglyceride Metabolism and Disease.
Molecular and Cellular Pharmacology, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada V6T 1Z3.
Min Suk
MS
Kim
Ying
Y
Wang
Brian
B
Rodrigues
D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D058065:Diabetic Cardiomyopathies / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism*; D006321:Heart / Q000503:physiopathology; D006801:Humans; D008071:Lipoprotein Lipase / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000201:enzymology; D014280:Triglycerides / Q000378:metabolism*
D005227:Fatty Acids; D014280:Triglycerides; D008071:Lipoprotein Lipase