Dapagliflozin promotes white adipose tissue browning though regulating angiogenesis in high fat induced obese mice

Abstract Browning of white adipose tissue (WAT) is become an appealing target for therapeutics in the treatment of obesity and related metabolic diseases. Dapagliflozin is widely used in the treatment of type 2 diabetes, and it is also found that the drug exhibits regulate systemic metabolism such as obesity, insulin resistance and hepatic steatosis. However, the precise role of dapagliflozin on WAT remodeling remains to be elucidated. The current study aimed to explore the role of dapagliflozin on WAT browning in high-fat diet (HFD)-induced obesity mouse. C57BL/6J male mice were used to establish obesity model by following feeding with HFD. The mice were randomly treated with or without dapagliflozin for the experimental observation. The volume and fat fraction of WAT were quantified, H&E staining and immunohistochemistry were conducted to investigate the white-to-brown fat conversion and adipose tissue angiogenesis in WAT respectively. qPCR was employed to explore the mRNA expression levels of genes involved in fat browning and angiogenesis in WAT. Subsequently, 3T3-L1 cells were used to explore the effect of dapagliflozin on preadipocytes differentiation in vitro. Our results demonstrated that dapagliflozin could reduce body weight gain and improve the metabolic phenotypes in HFD mice via regulating lipogenesis and angiogenesis of WAT. Furthermore, dapagliflozin reduce cells differentiation, up-regulate expression of WAT browning and angiogenesis genes in 3T3-L1 adipocytes in vitro. In conclusion, dapagliflozin promotes white adipose tissue browning in HFD induced obese mice via improving lipogenesis and angiogenesis in adipose tissue.