Grant: Project Grant

Reproductive dysfunction is a major health concern, where it is estimated that 16% of the Canadian couples affected. Reproduction is controlled by a number of external factors, which include nutritional status. It is well known that reproductive success is linked to nutritional and metabolic health. Yet the mechanisms by which nutritional status, whether through obesity or anorexia, directly influences the hypothalamic neurons that are responsible for reproduction are not yet studied. Our society has evolved to the state where obesity is prevalent, particularly in women and men of childbearing age. Obesity, mostly due to the ingestion of diets high in saturated fats or "bad fats", has reached epidemic levels in North America. Whether high-fat diet has a direct effect on the neurons responsible for reproductive function can be studied at a number of levels in my laboratory, from the cell to the whole animal, and from rodent models to humans. Exactly how the brain senses nutrients is not yet understood, but it is now recognized that the brain can sense fats and carbohydrates through specific neurons. 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 in specific models of reproductive neurons from female and male animals. We are also testing novel therapeutics to try to rescue the function of these neurons at the brain level using anti-inflammatory fatty acids or "good fats". Our research to explore how excess nutrients contributes to the manifestation of inflammation leading to reproductive disorders is an essential step for development of improved treatment regimens for infertility, obesity, and other related disorders, such as polycystic ovarian syndrome.