Heart disease is a major problem in the United States and across the world. Heart disease has been deemed the number one killer of both men and women. Many factors contribute to the development of heart disease, such as age, gender, and lifestyle factors. Efforts have been made aimed at promoting lifestyle modifications, such as diet and exercise, for the treatment and/or prevention of heart disease. In this regard, emphasis has been placed on methods to reduce obesity as it is a major contributor to the progression of heart disease. However, maintenance of such interventions have proven to be a major road block. Skeletal muscle (SKM) is a primary source of energy expenditure and it is now clear that it functions beyond muscle contraction. For example, SKM has the ability to secrete factors, termed 'myokines,' into the blood following exercise. One myokine, interluekin-15 (IL-15) shows potential in the fight against obesity because it has been linked to increases in energy expenditure. Although, it is clear that IL-15 could provide a potential route to treat and/or prevent obesity, its direct effects on the cardiovascular system are unknown. We have evidence that increases in circulating IL-15 can reduce fat mass, reduce lipid content in heart tissue, and increase expression of positive mediators of metabolism, such as peroxisome proliferator-activated receptor delta (PPARdelta) in multiple tissues. The overall goal of the proposed research is to firmly establish IL-15 as a myokine with the ability to treat and/or prevent obesity. It is hypothesized that IL-15-induced reductions of obesity will result in a reversal of heart disease. To examine our hypotheses genetically altered mouse and cell culture models will be used. It is anticipated that with pharmacological and genetic activation of IL-15, in mice, obesity will be reduced and in turn cardiovascular dysfunction will be reduced. We further expect that IL-15 induces metabolic processes through a complex signaling mechanism involving PPARdelta in cardiomyocytes. The studies proposed here will yield significant impact in the fight against obesity-induced heart dysfunction.
|Program type||Scientist Development Grant|
|Effective start/end date||07/01/2016 → 06/30/2019|