Exercising the Brain to Treat Obesity

"Obesity has become one of the most important clinical-epidemiological challenges facing our society. Obesity arises when the energy we intake as food chronically exceeds the energy we expend via exercise. Despite this simplistic overview the mechanisms underlying the development of obesity are incredibly complex.

It is well established that metabolic hormones such as leptin and insulin regulate our appetite and energy expenditure by signalling to neurons in an area of the brain termed the hypothalamus.

During the development of obesity, neurons in the hypothalamus become resistant to the actions of leptin and insulin which results in excessive food intake and attenuated energy expenditure. The development of leptin and insulin resistance within neurons of the hypothalamus is a critical mechanism underlying the development of obesity the development of drugs capable of reinstating leptin and insulin signalling at the forefront of metabolic research.

Physical activity contributes to the prevention and treatment of obesity, not only by increasing energy expenditure but also by modulating appetite and reducing food intake. Exciting new evidence shows that physical activity can re-sensitising hypothalamic neurons to the actions of leptin and insulin however the molecular mechanisms underlying this are not fully understood.

In this exciting project, you will use state of the art proteomic profiling (with space and time resolution) alongside transgenic mouse models of obesity and exercise training to evaluate the molecular mechanisms by which neurons of the hypothalamus become defective in obesity and how exercise restores them. The results of these studies will provide new insights into how exercise regulates neuronal functional, information that will be used to discover novel drug targets to treat obesity."