Influence of phthalates on glucose homeostasis and atherosclerosis in hyperlipidemic mice.

Abstract

BACKGROUND:

Phthalates 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.

METHODS:

To 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.

RESULTS:

Two 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.

CONCLUSION:

This 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.

• Authors: Wei Zhou, Mei-Hua Chen, Weibin Shi
• Journal: BMC endocrine disorders (BMC Endocr Disord) Vol. 15 Pg. 13 (Apr 02 2015) ISSN: 1472-6823 [Electronic] England
• PMID: 25881014 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Apolipoproteins E
• Blood Glucose
• Endocrine Disruptors
• Environmental Pollutants
• Phthalic Acids
• phthalic acid

Topics

• Animals
• Apolipoproteins E (genetics)
• Atherosclerosis (etiology, metabolism)
• Blood Glucose (drug effects, metabolism)
• Diabetes Mellitus, Type 2 (etiology, metabolism)
• Endocrine Disruptors (pharmacology)
• Environmental Pollutants (pharmacology)
• Female
• Homeostasis (drug effects)
• Hyperlipidemias (complications, genetics, metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Phthalic Acids (pharmacology)
• Risk Factors