Carnitine metabolism during fasting in dogs

Abstract

During starvation, a series of changes in whole body fuel use occur that result in conservation of fuel, particularly protein. Use of fat stores for ketone production and direct oxidation of fat as a primary fuel are characteristic of starvation. However, the mechanism by which this change develops is unclear. Carnitine is an important compound in the control of fat metabolism, since long-chain free fatty acids must be coupled with it to cross the mitochondrial membrane. This study attempts to define, in the fasting dog model, the interaction between plasma and muscle carnitine, its acyl esters, and the energy substrates available. Eight adult beagle dogs were studied during an 8-day period of starvation. Muscle and plasma were analyzed for free carnitine (FC), acid-soluble fraction, and long-chain esters (LCE), as well as substrate hormone profiles. Total carnitine (TC) and short-chain esters (SCE) were calculated. Muscle was analyzed for carnitine palmityl transferase activity (CPT). These measurements were performed on days 3, 5, and 8. There was a significant (p less than 0.05) loss in weight on days 3, 5, and 8. TC and FC increased significantly (p less 0.05) only on day 8; this occurred simultaneously with a significant (p less than 0.05) decrease in CPT. It was preceded by a significant (p less than 0.05) and persistent increase in plasma TC, FC, and LCE that developed on day 3. During starvation there was an increase in plasma carnitine levels before changes in muscle. The increase in muscle carnitine occurred between days 5 and 8 of starvation and seemed to be associated with a fall in CPT. This may be responsible either for or secondary to the decrease in metabolic rate that occurs during prolonged starvation.