The SCD inhibitor MTI-301 reduces steatohepatitis and ratio of C18:1/C18:0 levels in diet-induced murine models of MASH

Metabolic dysfunction-associated steatohepatitis (MASH) and metabolic dysfunction-associated steatotic liver disease (MASLD) develop because of fat disposition and excess accumulation of lipid droplets in hepatocytes and hepatic stellate cells. The endoplasmic reticulum enzyme stearoyl-CoA desaturase (SCD) is the rate-limiting enzyme that converts saturated fatty acids (SFAs) to monounsaturated fatty acids (MUFAs). MUFAs are an essential building block for triglycerides found in lipid droplet deposits in fatty livers. Increased deposit of triglycerides in the liver contributes to the sequelae of events, including inflammation and fibrosis, that culminates in the development of MASH. Due to the key role of SCD in lipid droplet formation, SCD is an attractive target for management of MASLD/MASH. Two independent diet induced MASH models were used to test the efficacy of the novel SCD inhibitor MTI-301. MTI-301 treatment decreased lipid droplets in both models, a finding that correlated with reduced desaturation indices (16:1/16:00 and 18:1/18:0) measured in the liver. Collectively our data suggests that the MTI-301 is an attractive drug for further development for the treatment of patients with fatty liver disease.