Hosting

Center for Research in Molecular Medicine and Chronic Disease (CiMUS)Organisation / Company: UNIVERSITY OF SANTIAGO DE COMPOSTELADepartment: Center for Research in Molecular Medicine and Chronic Disease (CiMUS)Laboratory: Neuroendocrinology, metabolism and cancerIs the Hosting related to staff position within a Research Infrastructure? NoAmbient temperature has a great impact on our energy homeostasis. Our previous results demonstrate the key role of TRPM8 ion channel, the most important cold sensor, in thermosensation, thermoregulation, and energy balance. Indeed, TRPM8-KO mice develop hypothermia and obesity under mild cooling. These results highlight the relevance of TRPM8 and ambient temperature as contributing factors in obesity and the metabolic syndrome beyond hypercaloric foods and sedentarism. Furthermore, TRPM8 activation emerges as a novel and attractive therapeutic strategy in obesity.In this proposal, we intend to gain further insight into the molecular mechanisms involved in the role of TRPM8 in the metabolic and circadian response to sustained cold temperature. We will characterize the contribution of TRPM8 in the activation of epigenomic, transcriptional, and circadian mechanisms underlying the adaptive reprogramming of metabolic regulation to sustained cold, including the study of a transgenerational effect. Furthermore, we will investigate new formulations for the delivery of TRPM8 agonists and new sources of TRPM8-activating compounds as effective therapeutic opportunities to combat obesity.In detail, we will study:The role of TRPM8 on the adaptive metabolic response to sustained cold ambient temperature, including changes in the epigenomic and transcriptional signature of brown adipose tissue (BAT).The effect of TRPM8 in cold-induced transgenerational regulation of energy homeostasis, focusing on paternal sperm methylome and the metabolism of the offspring.The functionality of a possible circadian interactome of Trpm8 and the clock gene Per2.New pharmaceutical formulations and new natural sources to activate TRPM8 as a therapeutic strategy in obesity.#J-18808-Ljbffr