Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on de novo fatty acid and cholesterol synthesis in the rat.

The effects of 1, 5, 10 and 20 micrograms/kg dosages of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) upon de novo fatty acid and cholesterol synthesis in liver and adipose tissue were determined in pair-fed rats. The incorporation of tritium from 3H2O into tissue lipids was measured. Hepatic and adipose fatty acid synthetic rates (mumoles acetyl units g-1 hr-1) in the control groups were 19.6 +/- 4 and 75.7 +/- 18.5, respectively, and the liver cholesterol synthetic rate was 2.9 +/- 0.5. TCDD (1 microgram/kg) inhibited fatty acid synthesis in the liver and adipose tissue, by 44% and 41%, respectively, and the liver cholesterol synthesis was inhibited by 37%. The extent of these inhibitions increased with increasing dosages of TCDD. The effect of TCDD on sterol synthesis in adipose tissue could not be determined, because the tritium incorporation into the sterol fraction in this tissue was not detectable.