PARATHYROID HORMONE IN THE CENTRAL CONTROL OF ENERGY METABOLISM

Obesity is a major public health concern, associated with numerous co-morbidities, leading to high and increasing mortality rates. The need for more efficient therapeutic strategies prompts extensive research to improve our understanding of energy homeostasis regulation. It is now well established that obesity results from an imbalance in energy homeostasis, which is largely controlled by the central nervous system (CNS), and more specifically by the hypothalamus, the major integrative center of endocrine and paracrine factors in the brain. Indeed, this region presents a high permeability to circulating factors, and expresses the vast majority of the hormonal receptors.
Among those receptors, we identified the presence of parathyroid hormone receptor 1 (PTH1R), mostly studied for its role as a major regulator of peripheral calcium homeostasis, but whose role in the CNS remains unknown. PTH1R is a G-coupled protein receptor that binds, among others, the endocrine parathyroid hormone (PTH). Here, we show that the PTH1R/PTH coupling system acts as a fine-tuning mechanism in hypothalamic AgRP neurons controlling the integration of systemic metabolic signals and the energy expenditure.
Exploring the molecular and cellular mode of action of this system, we show that PTH1R/PTH coupling system leads to modulation of the mitochondrial network and activity of AgRP neurons. These discoveries enhance our understanding of the physiological and cellular mechanisms driving obesity and metabolic syndrome.