CARNITINE SUPPLEMENTATION AMELIORATES THE STEATOSIS AND KETOSIS INDUCED BY PIVALATE IN RATS

These studies examined the effect in rats of carnitine supplementation on variables of fat metabolism altered by administration of sodium pi valate, a compound which induces a carnitine deficiency. Weanling male rats received 20 mmol/L sodium pivalate or 20 mmol/L sodium bicarbona te in their drinking water for 2 wk. They were food-deprived for 24 h, and to maximize fatty acid oxidation; were cold-stressed for 4 h. In Experiment 1, group 1 received the bicarbonate, group 2 received the p ivalate, group 3 received the pivalate and 0.46 mmol L-carnitine in th e diet/d, while group 4 received the pivalate and 0.95 mmol L-carnitin e in the diet/d. In Experiment 2, group 1 received unsupplemented drin king water, group 2 received the bicarbonate, group 3 received the piv alate, and group 4 received the pivalate and 0.95 mmol L-carnitine in the diet/d. Pivalate-treated rats given the low carnitine diet had pla sma and liver triglyceride levels (Experiment 1), plasma beta-hydroxyb utyrate concentrations (Experiments 1 and 2) and urinary dicarboxylic acid excretion (Experiment 2) significantly greater than those of cont rols (P < 0.05). The reduced tissue carnitine concentrations, starvati on ketosis and lipid accumulation in the liver are findings also repor ted for human secondary carnitine deficiency due to organic acidurias. Supplementing the diet with L-carnitine at the level of 0.95 mmol/d s ignificantly raised plasma and tissue carnitine concentrations and red uced the plasma beta-hydroxybutyrate and liver triglyceride concentrat ions to levels not significantly different than control values. Carnit ine supplementation ameliorates the degree of liver lipid accumulation and exaggerated starvation ketosis induced by pivalate.