Kyeongkyu Kim

Abstract Nuclear receptors are key effectors of metabolic programs; however, the contribution of co-regulatory complexes in maintaining metabolic homeostasis is not fully understood. Here, we show that modulation of the constitutive androstane receptor (CAR) by the co-repressor silencing mediator of retinoic acid and thyroid hormone receptors (SMRT) is required for bile acid (BA) homeostasis.

Abstract Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) represents a global health crisis associated with dysregulated hepatic triglyceride (TG) synthesis, oxidation and secretion. Despite progress in targeting hepatic lipid synthesis/oxidation for MASLD treatment and a well-documented relationship between circadian rhythms and lipid metabolism, the adaptive mechanisms coordinating TG secretion with circadian timing remain incompletely understood.

To determine the physiological roles of ROR? in the liver, we generated ROR?-floxed mice (ROR?f/f) by gene targeting in ES cells and crossed ROR? floxed mice with Albumin-Cre (Alb-Cre) mice to selectively create liver-specific Ror? conditional knockout (KO) mice (hereafter named ROR?LKO) (Fig. 1a, b). The mRNA and protein levels of endogenous hepatic ROR? were remarkably depleted in ROR?LKO mice compared with littermate controls (hereafter named ROR?f/f) (Fig. 1c–f).