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ß-Hydroxybutyrate Oxidation Is Reduced and Hepatic Balance of Ketone Bodies and Free Fatty Acids Is Unaltered in Carnitine-Depleted, Pivalate-Treated Rats^1,2,

Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48224 ^* Departments of Surgery, Michigan State University and Butterworth Hospital, Grand Rapids, MI 49503

These experiments were designed to determine whether carnitine depletion in the rat due to pivalate administration causes reduced ß-hydroxybutyrate oxidation and alterations in hepatic balance of ketone bodies and free fatty acids, relative to control rats. Male rats were given 20 mmol/L sodium pivalate for 2 wk to induce a secondary carnitine deficiency. Control animals were given 20 mmol/L sodium bicarbonate in their drinking water. In the ketone utilization experiment, rats were food-deprived for 24 h and infused with the sodium salt of ß-hydroxybutyrate to maintain total plasma ketone concentrations between 6.0 and 10.0 mmol/L. After a bolus of 3-hydroxy[3-¹⁴C]butyrate, the recovery of expired ¹⁴CO₂ collected during the ensuing 100 main was significantly lower in the pivalate-treated rats than in the controls (P < 0.05). In the second experiment, blood samples from pivalate-treated and control rats were collected from the abdominal aorta, portal vein and hepatic vein to determine the hepatic balance (hepatic input — hepatic output) of ketone bodies and free fatty acids. No significant differences were seen between the two treatment groups for either ketone bodies or free fatty acids. We conclude that the higher plasma ketone concentrations seen in food-deprived, pivalate-treated rats were due to a lower rate of ketone utilization. No evidence of pivalate influence upon ketone production was found.

KEY WORDS: • carnitine • pivalate • ß-hydroxybutyrate • hepatic balance • rats

¹ Supported in part by a grant from the Butterworth Foundation.

² 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.

³ To whom correspondence and reprint 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.