Abstract
Brown adipose tissue (BAT) increases energy expenditure and decreases plasma glucose and lipids, making it a potential target to decrease the risks of obesity, type 2 diabetes, and cardiovascular disease (CVD). BAT functions in an endocrine and autocrine manner to improve whole‐body metabolism, however the role of BAT in the cardiovascular system is unknown. Here, we determined that transplantation of BAT (+BAT) increases in vivo cardiac hemodynamics. Lipidomics analysis revealed that the lipokine most up‐regulated in +BAT mice was 12,13‐diHOME. 12,13‐diHOME acutely increases cardiac hemodynamics via direct effects on the cardiomyocyte. Furthermore, incubation of cardiomyocytes with 12,13‐diHOME increased mitochondrial respiration via the ryanodine receptor. The effects of 12,13‐diHOME were absent in NOS1−/− mice and cardiomyocytes. We found that 12,13‐diHOME is decreased in human patients with heart disease, and this was correlated with decreased ejection fraction. Our results suggest an endocrine role for BAT to enhance cardiac function that is mediated by regulation of calcium cycling via 12,13‐diHOME and NOS1.Support or Funding InformationR01‐HL138738, R01‐AG060542
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