Rescue of heart lipoprotein lipase-knockout mice confirms a role for triglyceride in optimal heart metabolism and function

Abstract

IJ.Rescue of heart lipoprotein lipase-knockout mice confirms a role for triglyceride in optimal heart metabolism and function. Am J Physiol Endocrinol Metab 305: E1339 -E1347, 2013. First published October 1, 2013; doi:10.1152/ajpendo.00349.2013.-Hearts utilize fatty acids as a primary source of energy. The sources of those lipids include free fatty acids and lipoprotein triglycerides. Deletion of the primary triglyceride-hydrolyzing enzyme lipoprotein lipase (LPL) leads to cardiac dysfunction. Whether heart LPL-knockout (hLPL0) mice are compromised due a deficiency in energetic substrates is unknown. To test whether alternative sources of energy will prevent cardiac dysfunction in hLPL0 mice, two different models were used to supply nonlipid energy. 1) hLPL0 mice were crossed with mice transgenically expressing GLUT1 in cardiomyocytes to increase glucose uptake into the heart; this cross-corrected cardiac dysfunction, reduced cardiac hypertrophy, and increased myocardial ATP. 2) Mice were randomly assigned to a sedentary or training group (swimming) at 3 mo of age, which leads to increased skeletal muscle production of lactate. hLPL0 mice had greater expression of the lactate transporter monocarboxylate transporter-1 (MCT-1) and increased cardiac lactate uptake. Compared with hearts from sedentary hLPL0 mice, hearts from trained hLPL0 mice had adaptive hypertrophy and improved cardiac function. We conclude that defective energy intake and not the reduced uptake of fat-soluble vitamins or cholesterol is responsible for cardiac dysfunction in hLPL0 mice. In addition, our studies suggest that adaptations in cardiac metabolism contribute to the beneficial effects of exercise on the myocardium of patients with heart failure. triglyceride; heart failure; glucose; lactate; energetics; glucose transporters IN THE HEALTHY ADULT HUMAN HEART, most of the energy required for normal cellular processes is derived from the uptake and oxidation of fatty acids (FAs), with the remainder being contributed by glucose, lactate, and amino acids (36). FAs are delivered to the heart either as free fatty acids (FFAs) conjugated to albumin or via lipoprotein lipase (LPL)-mediated hydrolysis of lipoproteins, with subsequent uptake by FAT/CD36, other FA transporters, and nonreceptor mediated pathways (5).Cardiomyocyte deletion of LPL (hLPL0) leading to reduced triglyceride (TG) lipolysis increased cardiac glucose uptake and reduced expression of several peroxisomal proliferatoractivated receptor (PPAR) regulated genes (1). hLPL0 hearts developed reduced ejection fraction (2) and were unable to compensate when subjected to increased afterload due to aortic coarctation or hypertension (56). These data suggest that TG is an important source of lipid for cardiac energy.In heart failure, traditional cardiac substrate usage of FAs is perturbed, and as a result the heart shifts away from FA oxidation to glucose utilization. These changes in heart energy use have been studied experimentally in isolated hearts using buffers containing FFAs (35). W...

Mechanism of Increased LDL (Low-Density Lipoprotein) and Decreased Triglycerides With SGLT2 (Sodium-Glucose Cotransporter 2) Inhibition

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Induced Pluripotent Stem Cells-Derived Mesenchymal Stem Cells Attenuate Cigarette Smoke-Induced Cardiac Remodeling and Dysfunction

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