Abstract：
Polycystic ovary syndrome (PCOS), a common endocrine disorder affecting premenopausal women, is associated with various metabolic consequences such as insulin resistance, hyperlipidemia, obesity, and type 2 diabetes mellitus (T2DM). Insulin sensitizers, such as metformin and pioglitazone, though effective, often leads to significant gastrointestinal adverse effects or weight gain, limiting its suitability for women with PCOS. There is an urgent need for safe, effective and affordable agents. Dapagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, enhances glucose elimination through urine, thereby reducing body weight and improving glucose and lipid metabolism. Nevertheless, it is not currently recommended as a therapeutic option for PCOS in clinical guidelines. In this study, we systematically examined the impact of dapagliflozin on an obese PCOS mouse model, focusing on alterations in glucose metabolism, adipose tissue morphology, and plasma lipid profile. Obese PCOS was induced in mice by continuous dihydrotestosterone (DHEA) injections over 21 days and high-fat diet (HFD) feeding. PCOS mice were then orally gavaged with dapagliflozin (1 mg/kg), metformin (50 mg/kg), or vehicle daily for 8 weeks, respectively. Our results demonstrated that dapagliflozin significantly prevented body weight gain and reduced fat mass in obese PCOS mice. Meanwhile, dapagliflozin treatment improved glucose tolerance and increased insulin sensitivity compared to the control PCOS mice. Furthermore, dapagliflozin significantly improved adipocyte accumulation and morphology in white adipose tissue, resulting in a normalized plasma lipid profile in PCOS mice. In conclusion, our results suggest that dapagliflozin is an effective agent in managing glucose and lipid metabolism disorders in obese PCOS mice.
摘要：
多囊卵巢综合征(PCOS),影响绝经前妇女的常见内分泌紊乱,与各种代谢后果有关，如胰岛素抵抗，高脂血症,肥胖，2型糖尿病（T2DM）。胰岛素增敏剂，如二甲双胍和吡格列酮，虽然有效,通常会导致严重的胃肠道不良反应或体重增加，限制其对PCOS女性的适用性。迫切需要安全，有效和负担得起的代理商。Dapagliflozin,钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂，通过尿液增强葡萄糖消除，从而减轻体重并改善葡萄糖和脂质代谢。然而，临床指南目前不推荐将其作为PCOS的治疗选择.在这项研究中,我们系统地研究了达格列净对肥胖PCOS小鼠模型的影响，关注葡萄糖代谢的改变，脂肪组织形态学,和血浆脂质分布。通过在21天内连续注射双氢睾酮(DHEA)和高脂肪饮食(HFD)喂养在小鼠中诱导肥胖PCOS。然后用达格列净（1mg/kg）口服PCOS小鼠，二甲双胍（50mg/kg），或车辆每天8周，分别。我们的结果表明，达格列净显著防止肥胖PCOS小鼠体重增加和脂肪量减少。同时,与对照PCOS小鼠相比,dapagliflozin治疗改善了葡萄糖耐量并增加了胰岛素敏感性.此外，dapagliflozin显着改善白色脂肪组织中脂肪细胞的积累和形态，导致PCOS小鼠血浆脂质分布正常化。总之,我们的结果表明,达格列净是治疗肥胖PCOS小鼠糖脂代谢紊乱的有效药物.
