Female mice exposed to low doses of dioxin during pregnancy and lactation have increased susceptibility to diet-induced obesity and diabetes
| Autor: | Mikayla A. Payant, Melissa J. Chee, Jennifer E. Bruin, Rayanna C Merhi, Myriam P Hoyeck, Geronimo Matteo, Diana I Martin Alfonso, Hannah L Blair, C Duncan Spencer, Melody Zhang |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Metabolic plasticity GDM gestational diabetes mellitus GTT glucose tolerance test Mice 0302 clinical medicine Pregnancy Insulin-Secreting Cells Lactation Insulin Glucose homeostasis heterocyclic compounds AhR aryl hydrocarbon receptor CO corn oil reproductive and urinary physiology Proinsulin 2. Zero hunger Diabetes 3. Good health medicine.anatomical_structure Liver Cyp cytochrome P450 Cyp1a1 cytochrome P450 1A1 Original Article Female Disease Susceptibility medicine.symptom lcsh:Internal medicine endocrine system medicine.medical_specialty Diabetes risk 030209 endocrinology & metabolism Diet High-Fat Dioxins 03 medical and health sciences Diabetes mellitus Internal medicine Diabetes Mellitus medicine Animals Obesity lcsh:RC31-1245 Molecular Biology Dioxin business.industry Beta cells Cell Biology medicine.disease Mice Inbred C57BL stomatognathic diseases Glucose 030104 developmental biology Endocrinology 13. Climate action POPs persistent organic pollutants TCDD 2 3 7 8-tetrachlorodibenzo-p-dioxin HFD high-fat diet ITT insulin tolerance test business Weight gain Corn oil |
| Zdroj: | Molecular Metabolism, Vol 42, Iss, Pp 101104-(2020) Molecular Metabolism |
| ISSN: | 2212-8778 |
| DOI: | 10.1016/j.molmet.2020.101104 |
| Popis: | Objective Exposure to persistent organic pollutants is consistently associated with increased diabetes risk in humans. We investigated the short- and long-term impact of transient low-dose dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) exposure during pregnancy and lactation on glucose homeostasis and beta cell function in female mice, including their response to a metabolic stressor later in life. Methods Female mice were injected with either corn oil (CO; vehicle control) or 20 ng/kg/d TCDD 2x/week throughout mating, pregnancy and lactation, and then tracked for 6–10 weeks after chemical exposure stopped. A subset of CO- and TCDD-exposed dams was then transferred to a 45% high-fat diet (HFD) or remained on a standard chow diet for an additional 11 weeks to assess the long-term effects of TCDD on adaptability to a metabolic stressor. To summarize, female mice were transiently exposed to TCDD and then subsequently tracked beyond when TCDD had been excreted to identify lasting metabolic effects of TCDD exposure. Results TCDD-exposed dams were hypoglycemic at birth but otherwise had normal glucose homeostasis during and post-TCDD exposure. However, TCDD-exposed dams on a chow diet were modestly heavier than controls starting 5 weeks after the last TCDD injection, and their weight gain accelerated after transitioning to a HFD. TCDD-exposed dams also had an accelerated onset of hyperglycemia, impaired glucose-induced plasma insulin levels, reduced islet size, increased MAFA-ve beta cells, and increased proinsulin accumulation following HFD feeding compared to controls. Overall, our study demonstrates that low-dose TCDD exposure during pregnancy has minimal effects on metabolism during the period of active exposure, but has detrimental long-term effects on metabolic adaptability to HFD feeding. Conclusions Our study suggests that transient low-dose TCDD exposure in female mice impairs metabolic adaptability to HFD feeding, demonstrating that dioxin exposure may be a contributing factor to obesity and diabetes pathogenesis in females. Highlights • Female mice exposed to TCDD during pregnancy are hypoglycemic at birth. • TCDD exposure promotes weight gain long after exposure ceases. • TCDD-exposed dams fed a high-fat diet have accelerated onset of glucose intolerance. • TCDDHFD dams have defects in islet morphology and beta cell function. |
| Databáze: | OpenAIRE |
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