University of California, San Francisco (UCSF)

Class IIa HDAC4 Activates PRDM16 to Regulate Beige Adipocyte Expansion

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Obesity results from disequilibrium between excess energy consumed through the diet versus energy expenditure through basal metabolism, physical activity, and adaptive thermogenesis. Unfortunately, education about diet and exercise seem not to be sufficient to meet this emergency and new therapies are urgently needed. Brown fat and beige fat have emerged as one really new approaches to prevent obesity and metabolic diseases. Energy balance is the biological homeostasis of energy in living organisms, which means energy intake from food equals energy expenditure. When energy intake exceeds energy expenditure, excess energy will be stored as fat in adipose and other metabolic tissues, eventually leading to obesity and further development into type II diabetes. Brown adipose tissue (BAT) is critical for thermoregulation and energy imbalance, and promoting BAT adaptive thermogenesis in humans has been proposed as an alternative to improve metabolic health. The thermogenic functionality in brown adipocytes is conferred by the uncoupling protein 1, Ucp1, which can disperse proton gradient across the mitochondrial membrane to produce heat instead of ATP. We are focused on establishing a novel relationship between BAT thermogenesis and systemic metabolism. Particularly, we have generated several mouse lines with mitochondrial-related protein ablated specifically in brown adipocytes. Using this model, we have demonstrated that mitochondrial electron transport chain proteome imbalance may be a key component underlying a new role for BAT.