Purpose of Review

To summarize evidence on the potential involvement of the osteoprotegerin (OPG)/receptor activator of nuclear factor-kappa B (NF-κΒ) ligand (RANKL)/receptor activator of NF-κΒ (RANK) axis in the pathogenesis of metabolic diseases.

Recent Findings

The OPG-RANKL-RANK axis, which has been originally involved in bone remodeling and osteoporosis, is now recognized as a potential contributor in the pathogenesis of obesity and its associated comorbidities, i.e., type 2 diabetes mellitus and nonalcoholic fatty liver disease. Besides bone, OPG and RANKL are also produced in adipose tissue and may be involved in the inflammatory process associated with obesity. Metabolically healthy obesity has been associated with lower circulating OPG concentrations, possibly representing a counteracting mechanism, while elevated serum OPG levels may reflect an increased risk of metabolic dysfunction or cardiovascular disease. OPG and RANKL have been also proposed as potential regulators of glucose metabolism and are potentially involved in the pathogenesis of type 2 diabetes mellitus. In clinical terms, type 2 diabetes mellitus has been consistently associated with increased serum OPG concentrations. With regard to nonalcoholic fatty liver disease, experimental data suggest a potential contribution of OPG and RANKL in hepatic steatosis, inflammation, and fibrosis; however, most clinical studies showed reduction in serum concentrations of OPG and RANKL.

Summary

The emerging contribution of the OPG-RANKL-RANK axis to the pathogenesis of obesity and its associated comorbidities warrants further investigation by mechanistic studies and may have potential diagnostic and therapeutic implications.

中文翻译：

---

骨保护素/核因子-Kappa B 受体激活剂 核因子-Kappa B 轴配体/受体激活剂在肥胖、2 型糖尿病和非酒精性脂肪肝中的作用

审查目的

总结关于骨保护素 (OPG)/核因子-κB 受体激活剂 (NF-κB) 配体 (RANKL)/NF-κB 受体激活剂 (RANK) 轴在代谢性疾病发病机制中潜在参与的证据。

最近的发现

OPG-RANKL-RANK 轴最初涉及骨重塑和骨质疏松症，现在被认为是肥胖及其相关合并症（即 2 型糖尿病和非酒精性脂肪肝）发病机制的潜在贡献者。除骨骼外，OPG 和 RANKL 也在脂肪组织中产生，并可能参与与肥胖相关的炎症过程。代谢健康的肥胖与较低的循环 OPG 浓度有关，可能代表一种抵消机制，而升高的血清 OPG 水平可能反映代谢功能障碍或心血管疾病的风险增加。OPG 和 RANKL 也被提议作为葡萄糖代谢的潜在调节剂，并可能参与 2 型糖尿病的发病机制。在临床上，2 型糖尿病一直与血清 OPG 浓度升高有关。关于非酒精性脂肪性肝病，实验数据表明 OPG 和 RANKL 在肝脂肪变性、炎症和纤维化中具有潜在作用；然而，大多数临床研究表明 OPG 和 RANKL 的血清浓度降低。

概括

OPG-RANKL-RANK 轴对肥胖及其相关并发症的发病机制的新贡献值得通过机制研究进一步调查，并可能具有潜在的诊断和治疗意义。