BAP1 Suppresses White Adipose Tissue Browning and Thermogenesis Through Deubiquitinating KDM1B

The expression of BRCA1-associated protein 1 (BAP1) is decreased in response to thermogenic stimuli, while it is increased in the context of obesity. The knockdown of BAP1 in the inguinal white adipose tissue in mice leads to an amelioration of obesity and associated metabolic disorders, an effect attributed to enhanced thermogenesis. BAP1 increases the stability of KDM1B by deubiquitination, allowing KDM1B to regulate the expression of browning-related genes by erasing histone H3K4me1/2 modifications. ASXL2 is essential for the interaction between BAP1 and KDM1B, as well as for the function of KDM1B in histone modification.