Effect of 1,3-Butanediol on Hepatic Fatty Acid Synthesis and Metabolite Levels in the Rat

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Abstract
The effect of 1,3-butanediol on hepatic fatty acid synthesis and metabolite levels in the rat was examined. Hepatic fatty acid synthesis was depressed in rats fed 1,3-butanediol. An intraperitoneal injection of 1,3-butanediol increased blood glucose levels but did not affect hepatic fatty acid synthesis in the rat. Addition of 1,3-butanediol to the incubation buffer depressed glucose, but not acetate, conversion to fatty acids by rat liver slices. Methylene blue inhibition of hepatic fatty acid synthesis was partially reversed by the addition of 1,3-butanediol to the incubation buffer. Hepatic β-hydroxybutyrate levels and the β-hydroxybutyrate:acetoacetate ratio were increased when 1,3-butanediol was fed. Lactate and pyruvate levels were lower in freeze-clamped liver preparations from rats fed 1,3-butanediol than those observed in control animals. Further, the lactate:pyruvate ratio was increased, suggesting that the hepatic cytoplasmic NADH/NAD+ ratio was increased. Hepatic long-chain acyl CoA levels were also increased when 1,3-butanediol was fed. It is suggested that the shift in the cytoplasmic redox state and the increase in hepatic long-chain acyl CoA levels are involved in the decrease in hepatic fatty acid synthesis observed when rats are fed 1,3-butanediol.

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