Changes in the subcellular distribution of free carnitine and its acyl derivatives in diabetic rat hearts following treatment with L-carnitine.

Abstract

Carnitine deficiency has been demonstrated in diabetic hearts, and it is also well known that L-carnitine administration has a beneficial effect on cardiac function. Carnitine treatment would be expected to reduce the accumulation of long-chain acylcarnitine. However, many reports have shown that myocardial long-chain acylcarnitine levels were increased following treatment with L-carnitine in whole-heart studies. Since acylcarnitine exists in both the mitochondrial and cytosolic compartments, it is difficult to investigate changes in subcellular distribution by studying whole-heart preparations. The present study investigated the myocardial subcellular distribution of carnitine and its acyl derivatives in diabetic rats with or without L-carnitine treatment. Approximately 90% of total cellular carnitine was located in the cytosol in the diabetic hearts. Both mitochondrial and cytosolic levels of free carnitine and short-chain acylcarnitine were significantly decreased in the diabetic heart. However, the mitochondrial level of long-chain acylcarnitine was significantly increased. L-carnitine treatment reduced the mitochondrial level of long-chain acylcarnitine, but the cytosolic level of long-chain acylcarnitine was significantly increased. These results show that L-carnitine treatment prevents the accumulation of long-chain acylcarnitine in the mitochondrial space and then reduces the detergent effect of long-chain acylcarnitine on the mitochondrial membrane. We suggest that it is a possible mechanism of the beneficial effect of L-carnitine treatment on the diabetic heart.