Endocrine Abstracts

Obesity incidence is continuously increasing worldwide. It does not solely result from excess calorie intake and sedentary lifestyle. Environmental endocrine disrupting chemicals (EDCs), could also be involved, deregulating fat storage and energy balance. Thyroid hormones (THs) play major role for maintaining energy balance. They are well known to control all aspects of metabolism, acting both centrally and in peripheral metabolic organs to control lipid and carbohydrate metabolism, as well as metabolic-cellular mechanisms such as mitochondrial activity and thermogenesis. The hypothalamus-pituitary-thyroid gland (HPT) axis, which controls both metabolism and TH homeostasis, is set up during development. Thus, any perinatal perturbation of this axis could have major metabolic consequences at the adult age. EDCs, such as TBBPA (a flame-retardant known to affect TH signalling) are detected in human amniotic fluid and milk, it hence poses a threat to early development of the hormonal systems. In a previous study, we have shown that exposure to TBBPA during gestation causes changes in HPT axis regulation shortly after birth, but the consequences of these perinatal changes on adult homeostasis were not investigated. Here, we studied if perinatal exposure to TBBPA interferes with the ability of two mouse strains with different thyroid and metabolic capacities, the C57BL/6J and the WSB/EiJ mice, to cope with high fat-high sucrose diet (HFHS, mimics Western diet) at the adult age. We compared the metabolic responses of these two strains to the chemical exposure and diet. Pregnant dams received 10 mg/kg/d TBBPA or vehicle for 4 weeks (last week of gestation through lactation). The progeny followed a HFHS diet from 2 to 6 months of age. We compared four groups for each strain: vehicle+control diet, vehicle+HFHS diet, TBBPA+control diet and TBBPA+HFHS diet. We have shown that TBBPA exposure transiently lowers the circulating thyroxine levels at young age but these levels were recovered at adult age. In C57BL/6J strain, perinatal TBBPA exposure combined with HFHS at adult age leads to more pronounced weight gain, perturbed glucose homeostasis and changes in adipose tissues (histological aspect and mitochondrial respiration assessed by Seahorse mitostress test), while WSB/EiJ mice do not experience these obesogenic effects of TBBPA. Our results reveal the obesogenic effect of a perinatal TBBPA exposure in a genetic background dependent manner, providing a proof of principle that perinatal period is very sensitive to environmentally relevant EDC exposure, and that interfering with the setup of thyroid axis during perinatal period could have dramatic consequences on health in adulthood.