Grant: Joint Canada-Israel Health Research Program

World Health Organization declared obesity and diabetes 21st century epidemic. About 40% of world population is suffering from these disorders, taking lives of ~3 millions worldwide every year. As effective treatments are lacking, these numbers continue to grow every year. Recently, COVID19 pandemic caused an additional surge in the number of people suffering from these metabolic disorders. The brain significantly contributes to these pathologies. The brain is isolated from the peripheral blood circulation by a barrier protecting it from the entrance of harmful substances (pathogenic or inflammatory agents) and preventing excessive fluctuations in the levels of circulating molecules. However, a few specialized brain areas located in the hypothalamus are not fully isolated from peripheral circulation and thus can sense the composition of the blood (e.g. glucose and hormones). These specialized brain areas are of key importance for the organism, as they respond to the circulating molecules by controlling vital functions, such as food intake and energy metabolism. Failure to sense the composition of the blood (glucose and hormones) by these areas leads to the development of obesity and type 2 diabetes. The proposed project aims to study the mechanisms regulating properties of the barrier in rodents. We will also investigate the role of the brain`s biological clock in the regulation of this barrier during active and resting periods to match the needs of the organism during activity and sleep. We will test if this barrier malfunctions in animals fed high fat/glucose diet, preventing circulating satiety molecules from entering the brain, leading to the unresponsiveness of the brain to satiety signals, and contributing to the development of obesity and type 2 diabetes. We will also study the role of systemic inflammation caused by infectious diseases (such as "cytokine storm" caused by COVID19) in the barrier malfunction, contributing to the severity of these pathologies.