RT Journal Article
SR Electronic
T1 Female mice exposed to low-doses of dioxin during pregnancy and lactation have increased susceptibility to diet-induced obesity and diabetes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.07.09.195552
DO 10.1101/2020.07.09.195552
A1 Hoyeck, Myriam P
A1 Merhi, Rayanna C
A1 Blair, Hannah
A1 Spencer, C Duncan
A1 Payant, Mikayla A
A1 Martin Alfonso, Diana I
A1 Zhang, Melody
A1 Matteo, Geronimo
A1 Chee, Melissa J
A1 Bruin, Jennifer E
YR 2020
UL http://biorxiv.org/content/early/2020/08/20/2020.07.09.195552.abstract
AB Objective Exposure to persistent organic pollutants is consistently associated with increased diabetes risk in humans. We investigated the short- and long-term impact of chronic low-dose dioxin (aka 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 were then transferred to a 45% high fat diet (HFD) or remained on standard chow diet for an additional 11 weeks to assess long-term effects of TCDD on adaptability to a metabolic stressor.Results Dioxin-exposed dams were hypoglycemic at birth but otherwise had normal glucose homeostasis during and post-dioxin exposure. However, dioxin-exposed dams on chow diet were modestly heavier than controls starting 5 weeks after the last dioxin injection, and their weight gain accelerated after transitioning to a HFD. Dioxin-exposed dams also had accelerated onset of hyperglycemia, dysregulated insulin secretion, reduced islet size, increased MAFA- beta cells, and increased proinsulin accumulation following HFD feeding compared to control dams.Conclusions Our mouse model suggests that chronic low-dose dioxin exposure may be a contributing factor to obesity and diabetes pathogenesis in females.Competing Interest StatementThe authors have declared no competing interest.AhRAryl hydrocarbon receptorCOCorn OilCypCytochrome P450Cyp1a1Cytochrome P450 1A1Cyp1a2Cytochrome P450 1A2GDMGestational diabetes mellitusGSISGlucose stimulated insulin secretionGTTGlucose tolerance testHFDHigh fat dietITTInsulin tolerance testPOPsPersistent Organic PollutantsTCDD2,3,7,8-tetrachlorodibenzo-p-dioxin