Grant: Travel Awards - Institute Community Support

Over 50% of adults are living with obesity or overweight. Compared to males, females are protected from the development of obesity-associated disease. However, females lose this protection with the onset of menopause. We aim to identify the mechanism by which pre-menopausal females are protected from obesity-related disease and how this protection is lost with menopause. We have found that the ability to form new fat cells is found intact in female mice, but not in males under obesogenic conditions and is mediated by estrogen. The inability to form new fat cells results in storage dysfunction which results in spillover of excess fat into the blood where it then deposits into the heart and other organs, driving the development of cardiovascular diseases. Our preliminary data has demonstrated that the formation of new fat cells may be regulated by inflammatory signaling. Macrophages are the major source of inflammatory signaling in the fat and we have found sex differences in the abundance of macrophages. Thus, we propose that macrophages regulate the formation of new fat cells in a sex-dependent manner that is regulated by estrogen in obesity. To investigate this, we will determine the impact of macrophages on fat cell formation by chemically removing the macrophages from the fat tissue over the course of a western-style diet. The formation of fat cells will be assessed in a 'Adipochaser' mouse model that identifies newly formed fat cells. We will assess this in male and female mice. To determine the role of estrogen we will utilize female mice that have undergone ovariectomy surgery to eliminate estrogen production and simulate menopause with or without administration of estrogen. This project will address the current knowledge gaps regarding the loss of protection against obesity-associated cardiometabolic disease at the onset of menopause. Overall, this work could uncover targets for potential therapeutics preventing the development of obesity-associated disease.