Project 462052

Obesity is a major global health concern, especially in Western society where it is estimated that 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 balance 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 nutrients through specific neurons. Of interest, one of the most prevalent saturated fatty acids in the body, palmitate, signals to the brain to regulate feeding by modulating the expression of neuropeptides. In excess, palmitate is considered an "obesogen" or something that can lead to obesity if dietary levels are not controlled. Another chemical prevalently found in plastics, bisphenol A (BPA), is an endocrine-disrupting compound that is also considered an obesogen. Obesity is linked to insulin resistance, often leading to other detrimental metabolic diseases. Interestingly, we have discovered molecules linked to high levels of palmitate and BPA that can in turn control our basic physiology. Blocking the action of these molecules, called microRNAs, could potentially restore normal energy homeostasis and help to prevent the development of obesity. Therefore major efforts are currently underway in my laboratory to dissect the brain pathways involved in this discovery and how obesity progresses, with the hope of discovering targets for the treatment of obesity and diabetes. 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. Our research to explore how we can prevent the progression to obesity is an essential step for development of improved treatment regimens, and will lead to far reaching and long-term cost benefits to the healthcare system.