ASCORBATE INDIRECTLY STIMULATES FATTY-ACID UTILIZATION IN PRIMARY CULTURED GUINEA-PIG HEPATOCYTES BY ENHANCING CARNITINE SYNTHESIS

L-Ascorbic acid is required for the synthesis of L-carnitine, which is essential for the oxidation of long-chain fatty acids. The purpose of this study was to investigate the role of ascorbate on the oxidation of long-chain fatty acids in primary cultured guinea-pig hepatocytes. The hepatocytes were incubated in medium containing carnitine in the presence or absence of fatty acids. Exogenous fatty acids had no influence on the uptake of total carnitine into cells, but they lowered the free carnitine and consequently raised the concentration of short-chain acyl carnitine. Furthermore, carnitine supplementation of the medium in the presence of fatty acids led to a decrease of triglycerides in cells and an increase in the secretion of beta-hydroxybutyrate. These changes were also induced by the supplementation of the medium with both ascorbate and the precursor of carnitine (gamma-butyrobetaine) in the presence of fatty acids, although either ascorbate of gamma-butyrobetaine alone had no effect. in addition, increasing the concentration of supplemental ascorbate resulted in an enhancement of ketogenesis and a decrease of triglyceride accumulation. These results suggest that ascorbate enhances carnitine synthesis, which in turn stimulates beta-oxidation of fatty acids.