on Nonalcoholic Steatohepatitis in Mice. PLoS ONE

Background & Aims In recent years, nonalcoholic steatohepatitis (NASH) has become a considerable health-care burden worldwide. Pathogenesis of NASH is associated with type 2 diabetes mellitus (T2DM) and insulin resistance. However, a specific drug to treat NASH is lacking. We inves-tigated the effect of the selective sodium glucose cotransporter 2 inhibitor (SGLT2I) ipragli-flozin on NASH in mice. Methods We used the Amylin liver NASH model (AMLN), which is a diet-induced model of NASH that results in obesity and T2DM. AMLN mice were fed an AMLN diet for 20 weeks. SGLT2I mice were fed an AMLN diet for 12 weeks and an AMLN diet with 40 mg ipragliflozin/kg for 8 weeks. Results AMLN mice showed steatosis, inflammation, and fibrosis in the liver as well as obesity and insulin resistance, features that are recognized in human NASH. Ipragliflozin improved insu-lin resistance and liver injury. Ipragliflozin decreased serum levels of free fatty acids, hepatic lipid content, the number of apoptotic cells, and areas of fibrosis; it also increased lipid out-flow from the liver. Conclusions Ipragliflozin improved the pathogenesis of NASH by reducing insulin resistance and lipotoxi-city in NASH-model mice. Our results suggest that ipragliflozin has a therapeutic effect on NASH with T2DM