Effects of di-(2-ethylhexyl)phthalate administration on carbohydrate and fatty acid metabolism in rat liver.

1. Rats were fed on a diet containing 0, 1, 2, or 4% di-(2-ethylhexyl)phthalate (DEHP), a widely used plasticizer, for four weeks. 2. The level of plasma triglyceride was decreased in both the 1% DEHP and the 2% DEHP groups maintained for 1 to 2 weeks, but that of cholesterol was not changed. Plasma free fatty acid and ketone bodies increased in all DEHP groups. 3. The level of blood glucose was depressed to about 80% in the 2% and the 4% DEHP groups. Liver glycogen decreased markedly. Isotopic incorporations of 14C from [2-14C]pyruvate into blood glucose and liver glycogen were decreased. The changes in the contents of intermediates in the liver indicate that gluconeogenesis is inhibited at the reaction(s) between 3-phosphoglycerate and fructose 1,6-diphosphate. 4. Hepatic fatty acid synthesis increased about 2-fold on DEHP administration. The content of phospholipid in the liver was increased, whereas that of triglyceride was decreased. The rate of phospholipid synthesis was increased, but that of triglyceride was not changed.