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Carnitine Supplementation Ameliorates the Steatosis and Ketosis Induced by Pivalate in Rats^1,2,3,

Peri B. Bianchi, Denis C. Lehotay^* and Alan T. Davis^,4

Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48224 ^* The Hospital for Sick Children, Toronto, Ontario, Canada M5G1X8 Departments of Surgery, Michigan State University and Butterworth Hospital, Grand Rapids, MI 49503

These studies examined the effect in rats of carnitine supplementation on variables of fat metabolism altered by administration of sodium pivalate, a compound which induces a carnitine deficiency. Weanling male rats received 20 mmol/L sodium pivalate or 20 mmol/L sodium bicarbonate 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 pivalate, group 3 received the pivalate and 0.46 mmol L-carnitine in the diet/d, while group 4 received the pivalate and 0.95 mmol L-carnitine in the diet/d. In Experiment 2, group 1 received unsupplemented drinking water, group 2 received the bicarbonate, group 3 received the pivalate, 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 plasma and liver triglyceride levels (Experiment 1), plasma ß-hydroxybutyrate concentrations (Experiments 1 and 2) and urinary dicarboxylic acid excretion (Experiment 2) significantly greater than those of controls (P < 0.05). The reduced tissue carnitine concentrations, starvation ketosis and lipid accumulation in the liver are findings also reported for human secondary carnitine deficiency due to organic acidurias. Supplementing the diet with L-carnitine at the level of 0.95 mmol/d significantly raised plasma and tissue carnitine concentrations and reduced the plasma ß-hydroxybutyrate and liver triglyceride concentrations to levels not significantly different than control values. Carnitine supplementation ameliorates the degree of liver lipid accumulation and exaggerated starvation ketosis induced by pivalate.

KEY WORDS: • carnitine • pivalate • ketosis • steatosis • rats

¹ Presented in part at Experimental Biology 1992, April 5–9, 1992, Anaheim, CA [Bianchi, P. B. & Davis, A. T. (1992) Carnitine (CN) supplementation ameliorates the steatosis and ketosis induced by pivalate. FASEB J. 6: A3282 (abs.)].

² Supported in part by a grant from the Butterworth Foundation.

³ The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

⁴ To whom correspondence and requests should be addressed at: Clinical Nutrition Laboratory, Butterworth Hospital, 100 Michigan NE, Grand Rapids, MI 49503.

Manuscript received 11 March 1996. Revision accepted 10 July 1996.