Exploring the impact of estrogen-related receptor gamma on metabolism and disease

Estrogen-related receptor gamma (ERR gamma) is a member of the ERR orphan nuclear receptor family which possesses three subtypes, alpha, R, and gamma. ERR gamma is reportedly predominantly expressed in metabolically active tissues and cells, which promotes positive and negative effects in different tissues. ERR gamma overexpression in the liver, pancreas, and thyroid cells is related to liver cancer, oxidative stress, reactive oxygen species (ROS) regulation, and carcinoma. Reduced ERR gamma expression in the brain, immune cells, tumor cells, and energy metabolism causes neurological dysfunction, gastric cancer, and obesity. ERR gamma is a constitutive receptor; however, its transcriptional activity also depends on co-regulators, agonists, and antagonists, which, when after forming a complex, can play a role in targeting and treating diseases. Moreover, ERR gamma has proven crucial in regulating cellular and metabolic activity. However, many functions mediated via ERR gamma remain unknown and require further exploration. Hence, considering the importance of ERR gamma, this review focuses on the critical findings and interactions between ERR gamma and co-regulators, agonists, and antagonists alongside its relationship with downstream and upstream signaling pathways and diseases. This review highlights new findings and provides a path to understanding the current ideas and future studies on ERR gamma-mediated cellular activity.