Morin, a novel liver X receptor α/β dual antagonist, has potent therapeutic efficacy for nonalcoholic fatty liver diseases.

Background And Purpose: Morin is a natural occurring flavonoid in many dietary plants and has a wide range of beneficial effects on metabolism; however, the mechanism underlying its action remains elusive.

Experimental Approach: A reporter assay and the time-resolved FRET assay were used to identify morin as a dual antagonist of liver X receptor (LXR)-α and -β. Morin (100 mg 100 g diet) was administered to high-fat diet-induced obese or LXRβ mice. The pharmacological effects and mechanism of action of morin were evaluated by Western blot and RT-PCR analyses.

Key Results: From the in vitro assays, morin was shown to be a dual antagonist of LXRα and LXRβ. In vivo, morin blunted the development of liver hepatic steatosis, reduced body weight gains, lowered triglyceride levels and improved glucose and insulin tolerance in mice fed a high-fat diet. Mechanistically, morin inhibited 3T3-L1 adipocyte differentiation and lipid formation in human hepatic HepG2 cells and suppressed the mRNA expression of genes downstream of LXR. Consistently, the effects of morin on metabolic disorders were attenuated in LXRβ mice.

Conclusion And Implications: Our data reveal that morin is a dual antagonist of LXRα and LXRβ and suggest that morin may alleviate hepatic steatosis and other associated metabolic disorders via the suppression of LXR signalling and, therefore, shows promise as a novel therapy or nutraceutical for nonalcoholic fatty liver disease.