ESTROGEN RELATED RECEPTOR GAMMA (ERRgamma) ENHANCES AND MAINTAINS BROWN FAT THERMOGENIC CAPACITY

摘要

Brown adipose tissue (BAT) plays a role in keeping an organism warm in response to a cold environment. In response to cold, transcription factors, including peroxisome proliferator receptor alpha (PGC1α), mediate the adaptive changes in the expression of oxidative and thermogenic genes in BAT. However, even without cold, BAT exhibits high expression of these genes relative to white adipose tissue (WAT). It is shown herein that estrogen related receptor gamma (ERRγ) is a critical factor that controls the expression of key metabolic genes in BAT under basal conditions. ERRγ is highly expressed in BAT versus WAT, yet is not transcriptionally induced by cold, suggesting it plays an important role in innate basal BAT function rather than in the adaptive response to cold. Based on these observations, methods of increasing thermogenesis in a subject by administering a therapeutically effective amount of one or more agents that increase ERRγ activity are provided.