Cardiovascular disease (CVD) is the leading cause of death in both men and women. The increasing rates of
CVD have increased the importance of elucidating potential therapeutic treatments for this disease. Brown
adipose tissue (BAT) is a thermogenic tissue that contains large amounts of mitochondria to dissipate chemical
energy as heat. BAT has a high capacity for both glucose and lipid oxidation, making BAT a potential target to
decrease plasma glucose and lipids and to protect against obesity and it's co-morbidities, including CVD.
Increasing the amount of BAT by transplantation improves metabolic health, reduces adiposity, and improves
heart function by increasing glucose uptake into the heart and providing a protective effect against
experimentally-induced myocardial infarction. Exercise is a well-established therapeutic tool to improve overall
heart health, and can also influence BAT activity. Our preliminary data demonstrate that exercise affects BAT
activity by altering the BAT lipidome, specifically by increasing the signaling lipid 12,13-diHOME. Injection of
this lipid into mice has a direct effect on the heart, increasing heart rate and left ventricular pressure. Taken
together, our exciting preliminary data show that 1) transplantation of BAT increases glucose uptake into the
heart; 2) exercise-training alters the lipid profile of BAT and increases the signaling lipid 12,13-diHOME; 3)
injection of 12,13-diHOME in mice directly affects heart function; and 4) 12,13-diHOME is significantly
increased after acute exercise in humans. These intriguing findings raise the possibility that BAT is involved in
tissue-tissue communication affecting the heart. Here, we will test the novel paradigm that BAT exerts
endocrine effects on the heart with three specific aims: 1) Determine if BAT exerts endocrine effects on the
heart; 2) Determine if 12,13-diHOME is responsible for BAT-induced endocrine effect on the heart; and 3)
Determine the mechanism through which 12,13-diHOME increases ventricular cardiomyocyte function and
metabolism. This project will establish if BAT enhances heart function and metabolism, and specifically the role
of the lipid 12,13-diHOME, which is released from BAT in response to exercise in both humans and rodents.
The proposed studies have the potential to elucidate novel BAT-induced signaling lipids that affect the heart,
which could be a new therapeutic approach to combat CVD.