beta-Hydroxybutyrate oxidation is reduced and hepatic balance of ketone bodies and free fatty acids is unaltered in carnitine-depleted, pivalate-treated rats

Abstract

These experiments were designed to determine whether carnitine depletion in the rat due to pivalate administration causes reduced beta-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 beta-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 min 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.