2021-05-18l Hit 3525
Nuclear receptors: Strategies for new therapeutic interventions against nonalcoholic fatty liver diseases
Mi-Ock Lee, Ph.D.
College of Pharmacy, Seoul National University, Korea
Non-alcoholic steatohepatitis (NASH) is closely associated with the metabolic complications as a result of overnutrition, including obesity and insulin resistance. Despite recent advances in understanding the pathogenesis of NASH, there are no Food and Drug Administration-approved pharmacotherapeutics that specifically target NASH. Retinoic acid-related orphan receptor (ROR) belongs to the nuclear hormone receptor superfamily that regulates diverse target genes that are associated with the regulation of lipid and cholesterol metabolic pathways in experimental animals and in human patients. Previously, we showed that activation of ROR dramatically attenuated diet-induced hepatic steatosis and inflammation in diet-induced NASH mouse models. Also, we demonstrated that ROR is a regulator of mitochondrial quality control in response to metabolic input. Importantly, the function of ROR is controlled by a synthetic ligand, JC1-40, which improved symptoms of NASH in mice. Today, I will show evidences that ROR and its lipidic ligands control M2 response of KCs under metabolic stress, and discuss the associated molecular mechanisms. Our data could provide new insights into the clinical application of the nuclear receptors and lipid mediators for the treatment of NASH.