Obesity is associated with lung function impairment and respiratory diseases; however, the underlying pathophysiological mechanisms are still elusive, and therapeutic options are limited. This study examined the effects of prolonged excess fat intake on lung mechanics and microstructure and tested spermidine supplementation and physical activity as intervention strategies. C57BL/6N mice fed control diet (10% fat) or high-fat diet (HFD; 60% fat) were left untreated or were supplemented with 3 mM spermidine, had access to running wheels for voluntary activity, or a combination of both. After 30 wk, lung mechanics was assessed, and left lungs were analyzed by design-based stereology. HFD exerted minor effects on lung mechanics and resulted in higher body weight and elevated lung, air, and septal volumes. The number of alveoli was higher in HFD-fed animals. This was accompanied by an increase in epithelial, but not endothelial, surface area. Moreover, air-blood barrier and endothelium were significantly thicker. Neither treatment affected HFD-related body weights. Spermidine lowered lung volumes as well as endothelial and air-blood barrier thicknesses toward control levels and substantially increased the endothelial surface area under HFD. Activity resulted in decreased volumes of lung, septa, and septal compartments but did not affect vascular changes in HFD-fed mice. The combination treatment showed no additive effect. In conclusion, excess fat consumption induced alveolar capillary remodeling indicative of impaired perfusion and gas diffusion. Spermidine alleviated obesity-related endothelial alterations, indicating a beneficial effect, whereas physical activity reduced lung volumes apparently by other, possibly systemic effects.

中文翻译：

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亚精胺的补充和自愿活动差异影响小鼠肺中与肥胖相关的结构变化。

肥胖与肺功能受损和呼吸系统疾病有关；然而，潜在的病理生理机制仍然难以捉摸，并且治疗选择受到限制。这项研究检查了延长脂肪摄入量对肺部力学和微观结构的影响，并测试了亚精胺补充和身体活动作为干预策略。饲喂对照饮食（10％脂肪）或高脂饮食（HFD； 60％脂肪）的C57BL / 6N小鼠不予治疗或补充3 mM亚精胺，可以自行行走以进行主动活动，或两者结合使用。30周后，评估肺力学，并通过基于设计的立体学对左肺进行分析。HFD对肺力学影响不大，导致体重增加，肺，空气和中隔容积增加。在HFD喂养的动物中，肺泡的数量更高。这伴随着上皮而不是内皮表面积的增加。此外，气血屏障和内皮明显增厚。两种治疗均不影响与HFD相关的体重。在HFD下，亚精胺降低了肺体积以及内皮和气血屏障的厚度，并显着增加了内皮表面积。活性导致肺，中隔和中隔室体积减少，但不影响HFD喂养小鼠的血管变化。联合处理未显示累加作用。总之，过多的脂肪消耗会导致肺泡毛细血管重构，提示灌注和气体扩散受损。亚精胺减轻了肥胖相关的内皮细胞改变，表明具有有益作用，