Adipogenesis, the process of white adipose tissue expansion, plays a critical role in the development of obesity. Osteoprotegerin (OPG), known for its role in bone metabolism regulation, emerges as a potential regulator in mediating adipogenesis during obesity onset. This study aims to elucidate the involvement of OPG in adipogenesis during the early phases of diet-induced obesity and explore its therapeutic potential in obesity management. Using a diet-induced obesity model, we investigated OPG expression patterns in adipocytes and explored the mechanisms underlying its involvement in adipogenesis. We also assessed the effects of targeted silencing of OPG and recombinant OPG administration on obesity progression and insulin resistance. Additionally, the impact of electroacupuncture treatment on OPG levels and obesity management was evaluated in both animal models and human participants. OPG expression was prominently activated in adipocytes of white adipose tissues during the early phase of diet-induced obesity. Hyperlipidemia induced Cbfa1-dependent OPG transcription, initiating and promoting adipogenesis, leading to cell-size expansion and lipid storage. Intracellular OPG physically bound to RAR and released the PPARɤ/RXR complex, activating adipogenesis-associated gene expression. Targeted silencing of OPG suppressed obesity development, while recombinant OPG administration promoted disease progression and insulin resistance in obese mice. Electroacupuncture treatment suppressed obesity development in an OPG-dependent manner and improved obesity parameters in obese human participants. OPG emerges as a key regulator in mediating adipogenesis during obesity development. Targeting OPG holds promise for the prevention and treatment of obesity, as evidenced by the efficacy of electroacupuncture treatment in modulating OPG levels and managing obesity-related outcomes.

中文翻译：

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骨保护素介导肥胖症的脂肪生成


脂肪生成，即白色脂肪组织扩张的过程，在肥胖的发展中起着至关重要的作用。骨保护素（OPG）以其在骨代谢调节中的作用而闻名，是肥胖发作期间介导脂肪生成的潜在调节剂。本研究旨在阐明 OPG 在饮食引起的肥胖早期阶段参与脂肪生成，并探讨其在肥胖管理中的治疗潜力。使用饮食诱导的肥胖模型，我们研究了脂肪细胞中的 OPG 表达模式，并探讨了其参与脂肪生成的机制。我们还评估了 OPG 靶向沉默和重组 OPG 给药对肥胖进展和胰岛素抵抗的影响。此外，在动物模型和人类参与者中评估了电针治疗对 OPG 水平和肥胖管理的影响。在饮食诱导肥胖的早期阶段，白色脂肪组织的脂肪细胞中 OPG 表达显着激活。高脂血症诱导 ​​Cbfa1 依赖性 OPG 转录，启动并促进脂肪生成，导致细胞大小扩张和脂质储存。细胞内 OPG 与 RAR 物理结合并释放 PPARɤ/RXR 复合物，激活脂肪生成相关基因表达。 OPG 的靶向沉默抑制了肥胖的发展，而重组 OPG 的给药则促进了肥胖小鼠的疾病进展和胰岛素抵抗。电针治疗以 OPG 依赖性方式抑制肥胖发展，并改善肥胖人类参与者的肥胖参数。 OPG 成为肥胖发展过程中介导脂肪生成的关键调节剂。 以 OPG 为靶点有望预防和治疗肥胖，电针治疗在调节 OPG 水平和管理肥胖相关结果方面的功效就证明了这一点。