Sodium glucose cotransporter 2 inhibitor dapagliflozin depressed adiposity and ameliorated hepatic steatosis in high-fat diet induced obese mice

With the increasing obesity prevalence, the rates of obesity-related diseases, including type 2 diabetes, non-alcoholic fatty liver disease (NAFLD), and cardiovascular diseases, have increased dramatically. Dapagliflozin, one of the sodium glucose cotransporter inhibitors, not only exerts hypoglycaemic effects through increasing urinary glucose excretion but alsoreprograms the metabolic system, leading to benefits in metabolic and cardiovascular diseases. In this study, pre-established obese mice on a high-fat diet were given dapagliflozin by gavage for fourweeks. It showed that dapagliflozin can enhance fat utilization and browning of adipose tissue and improve local oxidative stress, thus inhibiting fat accumulation and hepatic steatosis without disturbance in body weight or plasma glycolipid level. Overall, our study highlights the potential clinical application of SGLT2 inhibition in the prevention of obesity and related metabolic diseases, such as insulin resistance, NAFLD, and diabetes.随着肥胖患病率逐年攀升，肥胖相关疾病的发病率亦显著升高，此类疾病包括2型糖尿病、非酒精性脂肪性肝病（non-alcoholic fatty liver disease, NAFLD）以及心血管疾病。达格列净（dapagliflozin）作为钠-葡萄糖协同转运蛋白抑制剂（sodium glucose cotransporter inhibitors）的一员，不仅可通过增加尿糖排泄发挥降糖作用，还能重塑机体代谢系统，进而对代谢性疾病与心血管疾病产生有益效应。本研究中，研究人员对预先经高脂饮食诱导造模的肥胖小鼠连续4周给予达格列净灌胃干预。结果显示，达格列净可增强脂肪利用效率与脂肪组织褐变程度，改善局部氧化应激状态，从而抑制脂肪堆积与肝脂肪变性，且不会对小鼠体重及血浆糖脂水平产生干扰。综上，本研究揭示了SGLT2抑制疗法在肥胖及相关代谢性疾病（如胰岛素抵抗、非酒精性脂肪性肝病、糖尿病）预防中的潜在临床应用价值。