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Comparison among the Lipogenic Potential of various Substrates in Rat Hepatocytes: The Differential Effects of Fructose-Containing Diets on Hepatic Lipogenesis¹

Department of Physiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 93616

Fructose feeding has been reported to cause hypertriglyceridemia in rats. Apparently this is due to increased hepatic fatty acid synthesis. In hepatocytes from female rats fed a 60% sucrose or fructose diet, the rate of lipogenesis was two times higher than in cells from rats fed a 60% glucose diet and three times higher than in cells from rats fed a commercial nonpurified diet. In hepatocytes from rats fed the fructose-containing diets, lactate was a better substrate than either butyrate or acetate, whereas in cells from rats fed either the glucose diet or the nonpurified diet, butyrate was the best lipogenic substrate, and the lipogenic potential of lactate and acetate was similar. In all cases, 1 mM fructose caused a 30–40% stimulation of lipogenesis, while 10 mM glucose did not enhance fat synthesis above the endogenous rates. These results suggest that the differential effect of fructose-containing diets on hepatic lipogenesis results from activation of pyruvate dehydrogenase, thereby increasing the efficiency by which lactate is used as a carbon source for fatty acid synthesis. The differences in lipogenic potential of the various substrates tested is discussed.

KEY WORDS: • fatty acid synthesis • sterol synthesis • dietary carbohydrate • rat • hepatocytes • pyruvate dehydrogenase • fructose

¹ The authors dedicate this manuscript to the memory of Lucille S. Hurley, our friend and colleague.

² Sponsored by Consejo de Desarrollo Cienti'fico y Humani'stico, Universidad Central de Venezuela.

³ To whom correspondence should be addressed.

Manuscript received 2 December 1988. Revision accepted 21 April 1989.

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