Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on lipid synthesis and lipogenic enzymes in the rat

A single i.p. administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) caused within 1 wk of exposure a dose-dependent progressive inhibition of liver fatty acid synthetic rate with con-cornitant decreases in hepatic fatty acid synthetase and acetyl-coenzyme A carboxylase activities. Similarly, hepatic cholesterol synthetic rate was markedly inhibited with increasing dosage of TCDD, although the corresponding decrease in 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity was of lesser mag-nitude. Linear regression analyses of the reciprocals of the responses versus the dose revealed that the TCDD concentra-tion which caused 50 % inhibition of the activities of various lipogenic enzymes and of lipid synthetic rates ranged from 1 1 to 20 pg/kg (34-67 nM) with an average of 1 5 pg/kg (47 nM). Hepatic cholesterol synthesis seemed to be more sensitive to inhibition than fatty acid synthesis whether it was based o