Obesity, closely related to systematic metabolic disorders, has become a major public health problem in recent decades. Here, we aimed to study the function of Parathyroid hormone-related protein (PTHrP) on high fat diet (HFD) induced murine obesity. Male C57BL/6J mice were transduced with adeno-associated virus vector encoding PTHrP (AAV-PTHrP) or adeno-associated virus control vector (AAV-Vehicle), following with HFD for 8 weeks. In addition, mice without transduction were fed on normal diet or HFD, respectively. Histological, metabolic and biochemical changes were detected. At the endpoint of experiment, body weight of mice treated with AAV-PTHrP did not increase as much as mice with AAV-Vehicle, but similar as mice with normal diet. Food efficiency ratio and weight of interscapular brown adipose tissue and epididymal white adipose tissue in mice overexpressed PTHrP were also lower than mice transducted with AAV-Vehicle. Besides, administration of AAV-PTHrP inhibited HFD-induced adipocyte hypertrophy. Protein level of PKA signaling pathway and thermogenic gene in adipose tissue exhibited a significant raise in HFD + AAV-PTHrP group, whereas transcription of inflammatory gene were decreased. Additionally, PTHrP overexpression ameliorated HFD-induced dyslipidemia, hepatic steatosis and insulin sensitivity. In HFD-induced murine obesity model, PTHrP is crucial to maintain metabolic homeostasis. PTHrP drives white adipose tissue browning and inhibits whitening of brown adipose tissue. Most importantly, PTHrP prevented HFD-induced obesity, hepatic steatosis and insulin resistance.

肥胖与系统性代谢紊乱密切相关，已成为近几十年来的主要公共卫生问题。在这里，我们旨在研究甲状旁腺激素相关蛋白 (PTHrP) 在高脂饮食 (HFD) 诱导的小鼠肥胖中的作用。用编码 PTHrP 的腺相关病毒载体 (AAV-PTHrP) 或腺相关病毒对照载体 (AAV-Vehicle) 转导雄性 C57BL/6J 小鼠，然后用 HFD 转导 8 周。此外，没有转导的小鼠分别以正常饮食或HFD喂养。检测到组织学、代谢和生化变化。在实验结束时，用 AAV-PTHrP 治疗的小鼠的体重没有像用 AAV-Vehicle 治疗的小鼠那样增加，但与正常饮食的小鼠相似。过表达 PTHrP 的小鼠肩胛间棕色脂肪组织和附睾白色脂肪组织的食物效率比和重量也低于用 AAV-Vehicle 转导的小鼠。此外，施用 AAV-PTHrP 可抑制 HFD 诱导的脂肪细胞肥大。HFD+AAV-PTHrP组脂肪组织中PKA信号通路和产热基因的蛋白水平显着升高，而炎症基因的转录降低。此外，PTHrP 过表达改善了 HFD 诱导的血脂异常、肝脂肪变性和胰岛素敏感性。在 HFD 诱导的小鼠肥胖模型中，PTHrP 对维持代谢稳态至关重要。PTHrP 驱动白色脂肪组织褐变并抑制棕色脂肪组织变白。最重要的是，PTHrP 可预防 HFD 引起的肥胖、肝脂肪变性和胰岛素抵抗。