Objective

To explore how systemic factors that modify knee osteoarthritis risk are connected to ‘whole-joint’ structural changes by evaluating the effects of high-fat diet and wheel running exercise on synovial fluid (SF) metabolomics.

Methods

Male mice were fed a defined control or high-fat (60% kcal fat) diet from 6 to 52 weeks of age, and half the animals were housed with running wheels from 26 to 52 weeks of age (n = 9–13 per group). Joint tissue structure and osteoarthritis pathology were evaluated by histology and micro-computed tomography. Systemic metabolic and inflammatory changes were evaluated by body composition, glucose tolerance testing, and serum biomarkers. SF metabolites were analyzed by high performance-liquid chromatography mass spectrometry. We built correlation-based network models to evaluate the connectivity between systemic and local metabolic biomarkers and osteoarthritis structural pathology within each experimental group.

Results

High-fat diet caused moderate osteoarthritis, including cartilage pathology, synovitis and increased subchondral bone density. In contrast, voluntary exercise had a negligible effect on these joint structure components. 1,412 SF metabolite features were detected, with high-fat sedentary mice being the most distinct. Diet and activity uniquely altered SF metabolites attributed to amino acids, lipids, and steroids. Notably, high-fat diet increased network connections to systemic biomarkers such as interleukin-1β and glucose intolerance. In contrast, exercise increased local joint-level network connections, especially among subchondral bone features and SF metabolites.

Conclusion

Network mapping showed that obesity strengthened SF metabolite links to blood glucose and inflammation, whereas exercise strengthened SF metabolite links to subchondral bone structure.

中文翻译：

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长期运动和高脂肪饮食对小鼠滑液代谢组学和关节结构表型的影响：综合网络分析

 客观的

通过评估高脂肪饮食和跑轮运动对滑液（SF）代谢组学的影响，探讨改变膝骨关节炎风险的全身因素如何与“全关节”结构变化相关。

 方法

雄性小鼠在 6 至 52 周龄期间被喂食规定的对照或高脂肪（60% kcal 脂肪）饮食，一半的动物在 26 至 52 周龄期间被饲养在跑轮中（每组n = 9–13 ）。通过组织学和显微计算机断层扫描评估关节组织结构和骨关节炎病理学。通过身体成分、葡萄糖耐量测试和血清生物标志物评估全身代谢和炎症变化。通过高效液相色谱质谱法分析 SF 代谢物。我们建立了基于相关性的网络模型来评估每个实验组内全身和局部代谢生物标志物与骨关节炎结构病理学之间的连通性。

 结果

高脂肪饮食导致中度骨关节炎，包括软骨病理、滑膜炎和软骨下骨密度增加。相比之下，自愿锻炼对这些关节结构部件的影响可以忽略不计。检测到 1,412 种 SF 代谢物特征，其中高脂肪久坐小鼠最为明显。饮食和活动独特地改变了氨基酸、脂质和类固醇的 SF 代谢物。值得注意的是，高脂肪饮食增加了与白细胞介素-1β和葡萄糖不耐受等全身生物标志物的网络连接。相比之下，运动增加了局部关节级网络连接，尤其是软骨下骨特征和 SF 代谢物之间的连接。

 结论

网络图谱显示，肥胖增强了 SF 代谢物与血糖和炎症的联系，而运动则增强了 SF 代谢物与软骨下骨结构的联系。