Lipid biosynthesis was studied in vitro in liver, testes, and epididymal fat obtained from rats and rabbits fed di-(2-ethylhexyl)phthalate for 4 weeks at levels of 0.5% and 1.0%, respectively. Several differences in response of the two species to DEHP feeding were observed. In rats, but not in rabbits, DEHP feeding significantly reduced the incorporation of labeled mevalonic acid into total sterols (p <0.02), digitonin-precipitable sterols (p<0.01), and squalene (p<0.05). Inhibition of hepatic sterologenesis previously observed with DEHP feeding in the rat was also observed in the rabbit. In liver minces from the DEHP-fed rabbits, incorporation of3H-mevalonic acid into C27 sterols (cholesterol) and C30 sterols (lanosterol) was significantly reduced by about 40% (p<0.05 and p<0.01, respectively), whereas the incorporation of14C-glycerol 3-phosphate into phospholipids, and the combined fraction of monoglyceride + diglyceride, was significantly increased (p<0.001 and p<0.01, respectively). In studies with epididymal fat, DEHP feeding did not affect the total incorporation of14C-acetate or3H-mevalonate into total saponifiable and nonsaponifiable lipids of either the rat or rabbit. However, in the rat, significantly less of the14C-acetate (p<0.02) and3H-mevalonate (p<0.01) that was incorporated appeared in the combined fraction of cholesteryl ester + squalene. In addition, DEHP feeding significantly reduced serum cholesterol (p<0.01) in the rat but not in the rabbit. The results of this study indicate that DEHP feeding is associated with alterations in tissue lipid metabolism and that there are species differences in the response of tissues to DEHP.
All Science Journal Classification (ASJC) codes
- Organic Chemistry
- Cell Biology