In mammals, the maintenance of energy homeostasis relies on complex mechanisms requiring tight synchronization between peripheral organs and the brain. Thyroid hormones (THs), through their pleiotropi Show more
In mammals, the maintenance of energy homeostasis relies on complex mechanisms requiring tight synchronization between peripheral organs and the brain. Thyroid hormones (THs), through their pleiotropic actions, play a central role in these regulations. Hypothyroidism, which is characterized by low circulating TH levels, slows down the metabolism, which leads to a reduction in energy expenditure as well as in lipid and glucose metabolism. The objective of this study was to evaluate whether the metabolic deregulations induced by hypothyroidism could be avoided through regulatory mechanisms involved in metabolic flexibility. To this end, the response to induced hypothyroidism was compared in males from two mouse strains, the wild-derived WSB/EiJ mouse strain characterized by a diet-induced obesity (DIO) resistance due to its high metabolic flexibility phenotype and C57BL/6J mice, which are prone to DIO. The results show that propylthiouracil (PTU)-induced hypothyroidism led to metabolic deregulations, particularly a reduction in hepatic lipid synthesis in both strains. Furthermore, in contrast to the C57BL/6J mice, the WSB/EiJ mice were resistant to the metabolic dysregulations induced by hypothyroidism, mainly through enhanced lipid metabolism in their adipose tissue. Indeed, WSB/EiJ mice compensated for the decrease in hepatic lipid synthesis by mobilizing lipid reserves from white adipose tissue. Gene expression analysis revealed that hypothyroidism stimulated the hypothalamic orexigenic circuit in both strains, but there was unchanged melanocortin 4 receptor ( Show less
The obesity epidemic is well recognized as a significant global health issue. A better understanding of the energy homeostasis mechanisms could help to identify promising anti-obesity therapeutic stra Show more
The obesity epidemic is well recognized as a significant global health issue. A better understanding of the energy homeostasis mechanisms could help to identify promising anti-obesity therapeutic strategies. It is well established that the hypothalamus plays a pivotal role governing energy balance. The hypothalamus consists of tightly interconnected and specialized neurons that permit the sensing and integration of several peripheral inputs, including metabolic and hormonal signals for an appropriate physiological response. Current evidence shows that thyroid hormones (THs) constitute one of the key endocrine factors governing the regulation and the integration of metabolic homeostasis at the hypothalamic level. THs modulate numerous genes involved in the central control of metabolism, as Show less