The effect of various phthalate ester plasticizers on lipid metabolism in rats was studied in vivo and in vitro. Di-2-ethylhexyl phthalate (DEHP) and di-n-butyl phthalate (DBP) inhibited (30-70%) hepatic sterologenesis from 14C-acetate and 14C-mevalonate in liver minces from rats fed the phthalates at a level of 2.5 mmoles/100 g of chow diet for 21 days; inhibition of 14C-acetate incorporation into phospholipids, triglycerides, and steryl esters was reduced (35-70%) by DEHP and DBP feeding. In addition, serum cholesterol was lowered ca. 14 mg/dl with dietary DEHP or DBP but not with dimethyl phthalate (DMP). Hepatic total cholesterol levels were reduced significantly (31%, P<0.001) by DMP but not by DBP or DEHP. In other studies with DEHP fed at the 0.5% level in chow diets (1.3 mmoles/100 g), the incorporation (esterification) of 3H-oleate into di-and triglycerides was reduced ca. 40%. Furthermore, the addition of DEHP (2%, 5 mmoles/100 g) to a semisynthetic diet containing 10% fat (hydrogenated coconut oil) resulted in changes in serum lipoprotein composition. The percentage of serum cholesterol in LDL rose from 22% to 34% while that in HDL fell from 78% to 66%; these changes occurred without net changes in serum cholesterol levels. Possible mechanisms for the inhibitory effect of phthalates on hepatic lipid biosynthesis are discussed.
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 of 3H-mevalonic acid into C27 sterols (cholesterol) and C30sterols (lanosterol) was significantly reduced by about 40% (p <0.05 and p <0.01, respectively), whereas the incorporation of 14C-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 of 14Cacetate or 3H-mevalonate into total saponifiable and nonsaponifiable lipids of either the rat or rabbit. However, in the rat, significantly less of the 14C-acetate (p <0.02) and 3H-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.
The effect of di-2-ethylhexyl phthalate (DEHP) on lipid metabolism was studied in liver and brain from fetal rats taken 3 days before parturition from dams receiving dietary DEHP during gestation. In fetuses from rats receiving 0.5% or 1.0% DEHP in a stock diet, the incorporation of 14C-acetate and labeled mevalonate (3H or 14C) into the C27 sterols, C30 sterols, and squalene fractions of brain tissue incubated in vitro was significantly reduced between the confidence limits P <0.05 to P <0.001. When liver from fetuses was incubated with labeled mevalonate, incorporation of label into the C27 sterol and C30 sterol fractions was significantly reduced as well (P <0.02 to P <0.001), whereas incorporation of labeled mevalonate into the squalene fraction was not significantly altered. The incorporation of 14C-acetate into total hepatic lipids of the fetal rats was also studied, and statistically significant reductions in incorporation were observed in the lanosterol fraction (P <0.001), the combined fraction of sterol esters + squalene (P <0.02), and the combined fraction of cholesterol + diglycerides (P <0.01). No significant changes were observed in the incorporation of 14C-acetate into phospholipids, free fatty acids, or triglycerides. In 8-day old suckling rats delivered from dams fed 0.5% DEHP for the last 16 days of gestation and maintained on the same diet during the nursing period, the incorporation of 14C-mevalonate into hepatic C27 sterols, in vitro, was significantly depressed (P <0.05) whereas in corporation into C30 sterols and squalene was similar to control values. In these same suckling rats, body weights were significantly lower in the control group (21.7 vs. 18.8 g, P <0.01), whereas liver weight as a % of body weight was significantly higher (P <0.01) in rats nursing from the DEHP-fed dams. The results ind'teate that the inhibitory effect of dietary DEHP on lipid metabolism in the mature rat is transmitted across the placental barrier to the developing fetus and that the abnormal pattern of lipid metabolism in rats delivered from DEHP-fed females is only partially restored to normal during the suckling periods.
Serum triglycerides and serum total, esterified, and free (unesterified) carnitine were measured in 21 male Macaca arctoides that were switched from a low fat (5.2% w/w), high carbohydrate diet to a high fat (15.9% w/w), low carbohydrate diet for 90 days and then returned to the original low fat diet for a subsequent 76-day period. Serum triglycerides and total carnitine levels fell significantly (p less than 0.05) during the initial 2 wk of feeding the high fat diet and the ratio of esterified/unesterified carnitine rose significantly (P less than 0.05) on the high fat diet. A return to the low fat diet reversed these changes; triglycerides rose significantly (p less than 0.05) within 3 days and the ratio of esterified/unesterified carnitine fell significantly (p less than 0.05) within 3 days and the ratio of esterified/unesterified carnitine fell significantly (p less than 0.05) during the same period. A return of total carnitine levels to those initially observed on the low fat diet was slower to develop. Fasting for 24 to 48 h resulted in increases of 65 to 75% in total serum carnitine. This increase reflected elevations of both the esterified and unesterified carnitine fractions but was largely attributable to increases in esterified carnitine which rose from 10 to 41 nmol/ml by 48 h while unesterified carnitine rose from 55 to 72 nmol/ml during the same period. In addition, the ratio of esterified/unesterified carnitine ratio rose from 0.183 +/- 0.023 to 0.583 +/- 0.069 (n = 8) with a 48-h fast and was significantly correlated with serum beta-hydroxybutyrate levels at both 24 and 48 h.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.