Antiketonemic and antiketogenic actions of carnitine in vivo and in vitro in rats.

The effect of carnitine on ketone and lipid metabolism in intact rats and in isolated tissues was investigated. DL-Carnitine (200 mg/100 g body weight) administered orally lowered by approximately 40-65% plasma concentrations of ketone bodies in suckling rats and fasted adult rats. It also suppressed hyperketonemia induced by corn oil feeding in suckling and adult rats by approximately 30-60%. Carnitine did not change beta-hydroxybutyrate oxidation in heart and kidney mitochondria. Incubation of carnitine with tissue slices of cerebral cortex, kidney and diaphragm did not affect 14CO2 production or lipid synthesis from DL-[3-14C]-beta-hydroxybutyrate. The compound reduced the urinary concentration and excretion of ketone bodies in rats fed corn oil but had no effect in rats not treated with corn oil. Although DL-carnitine at concentrations ranging from 0.2 to 20 mM stimulated ketone production in hepatocytes, at a higher concentration (i.e., 40 mM) it produced a sharp depression in ketogenesis. These results indicate that carnitine does not stimulate ketone utilization by extrahepatic tissues. The antiketonemic effect of carnitine in rats treated with a high dose of the compound most likely results from inhibition of hepatic ketone production. An excessive increase in free carnitine by exogenous administration could upset the equilibrium fat conversion of acylcarnitine to acylCoA in mitochondria and hence suppress beta-oxidation and ketogenesis.