Emerging role of the orphan nuclear receptor estrogen-related receptor gamma in liver metabolic diseases

Abstract

Estrogen-related receptor gamma (ERRγ) is one of three members of the ERR family and remains an orphan, as there are no known natural ligands. ERRγ is an inducible transcription factor, and its ligand-independent transcriptional activity is regulated by co-regulator interactions and post-transcriptional modifications. Recent findings from animal models show that ERRγ, as a downstream mediator of multiple extracellular signals, plays a key role in coordinating endocrine and metabolic signals, resulting in changes in glucose, alcohol, lipid, and iron metabolism in the liver. Therefore, dysregulation of this receptor contributes to the pathogenesis of metabolic diseases such as hyperglycemia, insulin resistance, and alcoholic liver injury. Interestingly, ERRγ is also involved in responses to bacterial infection. These findings establish the importance of ERRγ in the endocrine and metabolic control of liver metabolism, and suggest that ERRγ may be a promising therapeutic target for metabolic diseases of the liver. Keywords: Orphan nuclear receptor, Estrogen-related receptor gamma (ERRγ), Gene regulation, Cell signaling, Liver metabolism