1146-P: The Effects of the SGLT2 Inhibitor Empagliflozin on Fatty Liver in Diet-Induced Obese Mice

Abstract

SGLT2 inhibitors (SGLT2Is), which are known to reduce blood glucose by inhibiting the reabsorption of renal glucose and promoting the excretion of urine glucose, are a kind of novel antidiabetic drugs for the treatment of type 2 diabetes and were reported to have multiple beneficial effects on the complications of diabetes. However, whether and how SGLT2Is improve obesity-related fatty liver remains unclear. In our study, 8-week-old C57BL/6 mice were fed on a normal diet or a high-fat diet for 16 weeks. After the diet induction, they were divided randomly into four groups: the normal chow diet group (NC group), the normal diet + empagliflozin group (NCE group), the high-fat diet group (HFD group) and the high-fat diet + empagliflozin group (HFDE group). The NCE group and the HFDE group were administered empagliflozin by oral gavage for 4 weeks, while the NC group and the HFD group were administered the same amount of cosolvent. After four-week treatment, body weight and fasting blood glucose of HFDE group were significantly improved when compared to HFD group. In addition, improved glucose tolerance and insulin sensitivity were observed in HFDE group. Both the energy intake and water intake increased significantly after empagliflozin intervention. What’s more, daily urine volume was remarkably increased by empagliflozin. Although there was no difference in total body fat mass between HFD group and HFDE group, the weight of subcutaneous adipose tissue and brown adipose tissue were significantly reduced. Importantly, liver weight was also statistically reduced in HFDE group compared with the HFD group. Oil red O staining showed that the hepatic steatosis in the HFDE group was ameliorated compared to HFD group. In conclusion, empagliflozin could significantly reduce the body weight and liver weight, and improve fasting blood glucose and hepatic steatosis. The underlying mechanism will be further explored. Disclosure W. Wang: None. W. Guo: None. Y. Jian: None. Y. Shen: None. F. Xu: None.