Effects of Aging and Dietary Carnitine on Myocardial Carnitine Concentration, Palmitate Oxidation, and Lipid Deposition.

Abstract

Carnitine concentration was measured in hearts frozen in situ and (1-('14)C) palmitate oxidation rate measured in whole heart homogenates from rats 6.5 and 18 months of age. Concentrations of total and free carnitine and long chain acylcarnitine were not different between age groups. Short and medium chain acylcarnitine concentration was 50% lower in hearts from 18 month rats, resulting in a 50% lower ratio of acetylcarnitine : free carnitine. A diet supplemented with 2% DL-carnitine resulted in a 100% higher concentration of short and medium chain acylcarnitine in hearts of 18 month old rats. The rates of palmitate oxidation were not different between age groups; addition of 1 mM L-carnitine to the incubation medium resulted in fivefold increases in palmitate oxidation rates in both age groups. These results indicate that (1) endogenous carnitine concentration is sufficient to support long chain fatty acid oxidation in hearts of 18 month old rats, and (2) the metabolic pathway from palmitate to CO(,2) and H(,2)O retains functional capacity between ages 6.5 and 18 months. Dietary carnitine manipulation affected only 18 month rats. Although a carnitine-free diet resulted in only slightly lower (less than 15%) myocardial concentrations of free and total carnitine and long chain acylcarnitine, the rate of palmitate oxidation was 77% higher in carnitine-free 18 month rats (CF18) compared to rats fed a diet supplemented with 2% DL-carnitine (CS18). Activity of carnitine palmitoyltransferase was 39% higher in CF18 hearts, which may explain the higher rate of palmitate oxidation. Morphometric analysis of electron micrographs showed that the percentage of cell volume occupied by lipid droplets was 55% higher in CF18 hearts than in CS18 hearts, indicating increased triglyceride synthesis in CF18 hearts. These results indicate (1) that in aging the liver and kidney retain their capacities for carnitine synthesis and the myocardium retains its capacity for carnitine uptake, and (2) in the aging myocardium there is a sensitivity of the entire fatty acid metabolic pathway to small changes in carnitine concentration.