Biological roles and developmental pathway of burn-induced beige fat in humans

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Project Summary/Abstract Beige adipocytes are an inducible form of thermogenic adipocytes that emerge in response to certain extrinsic stimuli, such as chronic cold exposure and burn injury (i.e., “browning” of white fat), and contribute to systemic glucose homeostasis. Given its inducible nature and relevance to adult humans, beige adipocytes have gained much attention as a potential therapeutic target in type 2 diabetes. This proposal is inspired by the recent findings that human subcutaneous white adipose tissue adopts a robust browning phenotype following a severe burn injury and that human beige fat possesses high capacity to oxidize glucose, fatty acids, and branched-chain amino acids (BCAA). The current objective is to extend our understandings on the biological roles and developmental pathway of human beige adipocytes in response to burn injuries. In Aim 1, we will test the hypothesis that the burn- induced beige fat functions as a “metabolic sink” not only for glucose, fatty acids but also for BCAA, which contributes to the prevention of post-burn hyperglycemia. In Aim 2, we will characterize molecular signatures of the burn-induced beige adipocytes at single-cell resolution and determine its developmental pathway. Our findings will have a significant impact because by use of the “burn model” we will determine the functional roles of WAT browning in the regulation of systemic glucose homeostasis and insulin resistance in humans. Our study will also develop the innovative concept that BAT is not simply a heat-generating organ but can also function as a metabolic sink for glucose, fatty acid, and BCAA.