Grant: Project Grant

Maintenance of body weight chiefly depends on a thermostat-like control system that measures fat mass and reports this measure to the brain centers that drive appetite. Fat mass is communicated to the brain by the hormone leptin which is produced by fat cells in proportion to the amount of fat: more fat leads to more leptin which in turn leads to less appetite, which thus allows for maintaining a set body weight much like a thermostat controls room temperature. The proposed research is aimed at elucidating the precise mechanism by which the hormone leptin enters the brain to act on the appetite regulating brain centers. We want to investigate if as we suspect circulating leptin makes blood vessels leaky in order to gain access to the brain. We want to further study if this leakiness depends on a specific brain cell type, the pericyte, which tightly enwraps brain vessels and is known to constrict the vessels they enwrap when engaged. If we indeed observe that leptin leads to vessel constriction and subsequent leakiness, we would have found a possible explanation why obesity is so strongly associated with neuroinflammation: it is due to increased vessel constriction and leakiness caused by the chronically high leptin levels of the obese state.