Hypertriglyceridemia and fatty liver of fasting rats after administration of emeriamine.

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The effect of emeriamine, a potent inhibitor of the entry of fatty acids into mitochondria on lipid metabolism, was examined. Emeriamine (10 mg/kg body weight) was orally administered to rats under the two different physiological conditions of a 2-day fast or refeeding with a high-carbohydrate diet after a 2-day fast. When rats were refed with a high-carbohydrate diet, serum and hepatic ketone bodies and the levels of free fatty acids decreased, and triglycerides significantly increased compared with fasting rats. However, no significant effect of emeriamine on serum and hepatic lipids was observed between two refeeding groups with or without emeriamine. Conversely, when emeriamine was administered to fasting rats, the levels of serum and hepatic triglycerides increased about 11- and 5-fold, respectively. However, the increased level of hepatic triglycerides was not accompanied by the activities of fatty acid synthetase and NADPH-generating enzymes. The analysis of serum lipoprotein revealed that very low-density lipoprotein consisted of triglyceride-rich particles and there were less apolipoproteins in the fasting rat given emeriamine. We also determined the 120-kDA protein content, which was probably dependent on lipogenesis. The level of 120-kDa protein was greatly increased with or without the administration of emeriamine after refeeding with a high-carbohydrate diet, but the concentration of 120-kDa protein was slight in the fasting rat with emeriamine. These results suggest that specific inhibition of fatty acid oxidation by emeriamine diverted the exogenous fatty acid to the esterification pathway, and induced fatty liver and hypertriglyceridemia under fasting conditions.