Pinealocyte-derived melatonin: a chronobiotic hormone that modulates the effects of photoperiod on energy homeostasis and metabolic dysfunctions
This project is part of the Université Laval / Université Côte-d'Azur research partnership.
Circadian and sleep/wake rhythms influence energy homeostasis and metabolism in various ways and their proper control is of prime importance in the maintenance of health. Indeed, disruption of circadian and sleep/wake rhythms can lead to health problems such as obesity and obesity-associated complications. Circadian and sleep/wake rhythms are influenced by environment factors, including seasonal changes, which, in the North, markedly affect the length of the photoperiod. Those rhythms are in large part controlled by the brain, specifically through the hypothalamic suprachiasmatic nucleus (SCN)- superior cervical ganglion (SCG)-pineal gland axis, which controls, via adrenergic receptors, the production of chronobiotic hormone melatonin. Melatonin is produced during the night and acts in the brain, pancreas, gut and adipose tissue to regulate energy homeostasis and metabolism.
Arrhythmicity in melatonin production leads to metabolic dysfunctions via mechanisms that need to be further explored. Consequently, we propose to investigate the pathways and mechanisms whereby perturbed pinealocyte-derived melatonin modulates energy homeostasis and metabolic dysfunctions (the three specific aims of the program are enunciated below). Using the powerful chemogenetic technology, we intend to exploit the signalling pathway of the pinealocyte adrenergic system to modulate the melatonin production in free-living lean and obese mice. We propose to measure a series of relevant metabolic, behavioural, neurobiological variables that are listed below. The program will be led by four established scientists emerging from two prominent institutions, namely, Institut de Pharmacologie Moléculaire et Cellulaire de Valbonne (IPMC) and Institut Universitaire de Cardiologie et de Pneumologie de Québec (IUCPQ) and sharing transdisciplinary and complementary expertise in physiology, molecular and cellular biology, neuroendocrinology, neuropharmacology and cellular and molecular neuroscience.