Maternal thyroid hormone receptor activation in mice sparks brown fat thermogenesis in the offspring

It is well established that maternal thyroid hormones play an important role for the developing fetus; however, the consequences of maternal hyperthyroidism for the offspring remain poorly understood. Here we show in mice that maternal 3,3',5-triiodothyronine (T3) treatment during pregnancy leads to improved glucose tolerance in the adult male offspring and hyperactivity of brown adipose tissue (BAT) thermogenesis in both sexes starting early after birth. The activated BAT provides advantages upon cold exposure, reducing the strain on other thermogenic organs like muscle. This maternal BAT programming requires intact maternal thyroid hormone receptor beta (TR beta) signaling, as offspring of mothers lacking this receptor display the opposite phenotype. On the molecular level, we identify distinct T3 induced alterations in maternal serum metabolites, including choline, a key metabolite for healthy pregnancy. Taken together, our results connect maternal TR beta activation to the fetal programming of a thermoregulatory phenotype in the offspring. Maternal thyroid hormone is important for fetal development. Here, the authors show that hyperthyroidism during pregnancy can program the offsprings' glucose sensitivity and response to cold via activation of maternal thyroid hormone receptor beta in a sex dependent manner