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Ascorbate Indirectly Stimulates Fatty Acid Utilization in Primary Cultured Guinea Pig Hepatocytes by Enhancing Carnitine Synthesis^1,2,3,

Rice Utilization Research Center, Korea Food Research Institute, Seognam-Si, Kyonggi-Do, Korea, 463-420; ^* Department of Nutrition and Food Science, Ochanomizu University, Bunkyo-ku, Tokyo 112, Japan

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 ß-hydroxybutyrate. These changes were also induced by the supplementation of the medium with both ascorbate and the precursor of carnitine (-butyrobetaine) in the presence of fatty acids, although either ascorbate of -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 ß-oxidation of fatty acids.

KEY WORDS: • fatty acids • guinea pigs • ascorbate • carnitine • triglycerides

¹ A partial report of this work was presented at the First International Congress on Vitamins and Biofactors in Life Science, September 16–20, 1991, Kobe, Japan [Ha, T. Y., Otsuka, M. & Arakawa, N. (1991) The stimulation of fatty acid oxidation in primary cultured guinea pig hepatocytes by carnitine and ascorbate, p. 96 (abs.)].

² Supported in part by a grant from the Uehara Memorial 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 should be addressed.

Manuscript received 10 June 1993. Revision accepted 5 January 1994.