Grant: Project Grant

Increased metabolism is one of the central causes for burn patients to have poor outcomes or die. These persistent metabolic changes accelerate the breakdown of fat and muscle tissues, increasing the risks of infections, sepsis and death. We and others have recently shown that browning of the white adipose tissue occurs after burn and is thought to contribute to chronic hypermetabolism. Uncoupling of mitochondria when adipose browns and converts to a beige phenotype increases energy expenditure by producing heat rather than adenosine triphosphate, the universal energy currency. Moreover, this beige adipose tissue demonstrates markedly increased lipid breakdown, releasing free fatty acids into circulation. Deposition of free fatty acids in downstream organs such as the liver and muscle further exacerbates organ dysfunction. For instance, hepatomegaly and fatty liver are often observed in burn patients, limiting the ability of this central metabolic organ to regulate biological processes and detoxify noxious compounds. As such, we hypothesize that the upstream adipose browning response is the central modulator for post-burn hypermetabolism. We will test our hypothesis using specific aims to identify systemic sequelae following adipose browning, cellular mediators of browning and ultimately, answer the question of whether browning and beige adipose tissue is beneficial or detrimental. The relevance of this project is that we could possibly identify the major mediator for post-burn hypermetabolism that is associated with poor outcomes in burn patients. Moreover, pharmaceutical stratagems which target the browning of white adipose post-burn may improve patient outcomes following this severe traumatic event.