Grant: Operating Grant

Obesity is a major global health concern, especially in Western society where it is estimated that 30% of the population is estimated to be obese and 65% of the population is overweight. Obesity is a major risk factor for other disorders, including diabetes, hypertension, and heart disease. A complex neuronal system has evolved to maintain energy homeostasis required for a healthy body weight, but it is biased towards weight gain in times of plenty. Exactly how the brain senses nutrients is not yet understood, but it is now recognized that the brain can sense fat and carbohydrates through specific neurons. On the other hand, insulin acts as a signal to regulate feeding and energy balance by modulating the expression of neuropeptides in the brain. However, insulin resistance, often caused by excess levels of fat and sugar intake, is a tremendous problem in the fight against obesity, often leading to the evolution of type 2 diabetes, Interestingly, it has been found that the brain produces an inflammatory response when exposed to high levels of fat. Therefore major efforts are currently underway in my laboratory to dissect the brain pathways involved in sensing nutrients and how insulin resistance develops, with the hope of discovering targets for the treatment of obesity. We are also testing novel therapeutics to try to rescue insulin resistance at the brain level. We have developed a number of unique neuronal cell models to study these pathways at the cellular level in tremendous detail, not yet possible in the animal model. Nutrients are recognized by the brain and are key regulators of weight maintenance. Our research to explore how excess nutrient intake contributes to the development of obesity is an essential step for development of improved treatment regimens for the current obesity epidemic, and will lead to far-reaching and long-term cost benefits to the healthcare system.