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.