Influence of phthalates on glucose homeostasis and atherosclerosis in hyperlipidemic mice

Abstract

BackgroundPhthalates are widely used as plasticizer and are considered as a typical endocrine-disrupting chemical. Epidemiological studies have associated serum or urinary phthalate metabolites with the prevalence of type 2 diabetes or related phenotypes. However, direct evidence supporting a causal role for exposure to phthalates in type 2 diabetes is lacking.MethodsTo determine the potential influence of phthalates on glucose homeostasis and atherosclerosis, female apolipoprotein E-deficient (Apoe−/−) mice were started at 6 weeks of age on a Western diet together with or without Bis-(2-ethylhexyl) phthalate. Phthalate was administered in drinking water at a daily dosage of 100 mg/kg. We examined glucose and insulin tolerance, plasma glucose and triglyceride levels, body weight, and atherosclerotic lesions in the aortic root.ResultsTwo weeks after treatment, phthalate-exposed mice had significantly higher fasting blood glucose level (97.9 ± 2.1 vs. 84.3 ± 5.3 mg/dl, P = 0.034) and exhibited a trend of increased glucose intolerance compared to control mice. Insulin tolerance test on non-fasted mice 3 weeks after treatment revealed that phthalate had little influence on insulin sensitivity though phthalate-treated mice had a higher glucose concentration (159.2 ± 6.0 vs. 145.2 ± 3.6 mg/dl; P = 0.086). On the Western diet, Apoe−/− mice showed a time-dependent rise in fasting plasma glucose and triglyceride levels. However, no significant differences were observed between phthalate-treated and control mice in either phenotype after 4, 8, and 12 weeks of phthalate exposure. Neither body weight nor atherosclerotic lesions of Apoe−/− mice was affected.ConclusionThis study indicates that exposure to phthalates gives rise to a brief interference of glucose homeostasis but has little impact on the development of type 2 diabetes and atherosclerosis in Apoe−/− mice.

Phytochemical and bioactive compounds identification of Ocimum tenuiflorum leaves of methanol extract and its fraction with an anti-diabetic potential

“…[36] However, the influence of phthalates on glucose homeostasis and atherosclerosis in hyperlipidemic mice was reported. [37] Previous studies indicate that the synthetic glycolipid OCH can prevent insulin and diabetes in non-obese diabetic mice. [38] However, till now, researchers have not reported anti-diabetic effect of di-n-butyl phthalate and pedunculin, 4,4′-methylene-bis(2-methylaniline), isosakuranetin (flavanone), and robinetin trimethyl ether (flavonoids).…”

Genetic linkage of hyperglycemia and dyslipidemia in an intercross between BALB/cJ and SM/J Apoe-deficient mouse strains

“…Plasma lipid levels, especially non-HDL cholesterol, of the F 2 mice were significantly elevated on the Western diet, so were the fasting glucose levels. When fed the Western diet, Apoe −/− mice display a rapid rise in non-HDL cholesterol levels, often reaching their peak within a couple of weeks (unpublished data), whereas their blood glucose levels rise more slowly and gradually within 12 weeks [ 43 , 44 ]. This difference in onset suggests a causal role for plasma lipids in the rise of blood glucose in the Apoe −/− mouse model.…”

Genetic basis underlying connection between hyperglycemia and dyslipidemia inApoe-deficient mice

“…When fed the Western diet, Apoe -/- mice display a rapid rise in non-HDL cholesterol levels, often reaching a plateau within a couple of weeks (unpublished data), whereas their blood glucose levels rise more slowly and gradually within 12 weeks (Li et al . 2012),(Zhou et al . 2015).…”