Ucp1-independent functions in brown and beige adipocytes

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ABSTRACT Uncoupling protein 1/Ucp1-mediated adaptive thermogenesis in brown adipose tissue/BAT is essential for thermoregulation and energy balance. Increasing adaptive thermogenesis in human brown fat has been considered as an alternative strategy to increase energy expenditure, and ultimately to improve metabolic health, since brown fat activity gradually declines with aging and metabolic diseases. Our previous work identified a unique phenomenon that brown adipocyte-specific Lrpprc knockout mice can trade off mitochondria-fueled Ucp1-dependent thermogenesis in BAT for systemic metabolic fitness. This proposal will use this new mouse model to investigate Ucp1-independent functions. Aim 1 will investigate the underlying mechanisms of the ATF4-driven thermogenesis in brown adipocytes. Aim 2 will determine the physiological regulation of this process. Aim 3 will address its metabolic contributions to systemic metabolism. Collectively, this proposal will reveal novel functions of brown (and/or beige) adipocytes beyond Ucp1-dependent thermogenesis.