Project 180531

The mechanisms linking male-pattern obesity to metabolic diseases such as diabetes and heart disease have not been fully elucidated but they may include chronic inflammation of fat tissue and an altered ability to adequately store excess dietary fats. Hormones called prostaglandins are recognized mediators of inflammation in many organs and they are also produced in fat tissue. However, we do not know whether they actually mediate part of the link between male-pattern obesity, fat tissue inflammation and the risk for metabolic disease. The objective of the proposal is to examine whether prostaglandins mediate the effects of male-pattern obesity and fat tissue inflammation on predictors of metabolic disease in women. Our hypothesis is that prostaglandin synthesis in fat tissue is a critical marker of male-pattern obesity and that prostaglandins actually mediate part of the link between male-pattern obesity, fat tissue inflammation and predictors of metabolic disease. To study visceral fat in humans, one needs to access the abdominal cavity during surgery under general anaesthesia. We have developed collaborations with gynecologists who help us invite their patients undergoing abdominal ablation of the uterus to participate in our studies. As in our past studies in this population, we will recruit 60 women undergoing such surgeries and we will test our hypothesis using a large number of measures performed in these women and their biological samples (blood and fat tissue). If prostaglandins do mediate part of the link between male-pattern obesity, fat tissue inflammation and metabolic disease, then drugs which modulate prostaglandin synthesis may help restore adipose tissue function and improve metabolic disease risk.