a Centre of Inflammation and Metabolism (CIM) and Centre for Physical Activity Research (CFAS) , Copenhagen University Hospital, University of Copenhagen , Copenhagen , Denmark.
b Department of Surgical Gastroenterology C , Rigshospitalet , Copenhagen , Denmark.
Acta Oncol. 2019 May;58(5):579-587. doi: 10.1080/0284186X.2018.1558371. Epub 2019 Jan 30.
Exercise may improve depression in cancer patients, yet the molecular mechanism behind this protection is poorly understood. Here, we aimed to explore the link between exercise and regulation of kynurenine (Kyn) metabolism and inflammation in patients with operable gastro-esophageal junction (GEJ) cancer patients, who improved significantly in depression score with exercise training. Fifty GEJ cancer patients were allocated to 12 weeks of supervised training twice weekly including interval-based aerobic exercise and resistance training, or standard care. Depression score was evaluated by HADS, and blood samples and muscle biopsies were collected for determination of Kyn metabolism and inflammation across the intervention. Depression scores decreased by -1.3 points in the exercise group ( < 0.01), whereas no changes were observed in the control group. Plasma 3-hydroxykynurenine (HK), a Kyn metabolite giving rise to other neurotoxic metabolites, increased by 48% ( <0.001) in the control group, while exercise training attenuated this accumulation. The production of HK is induced by inflammation, and while we observed no differences in systemic pro-inflammatory cytokines, exercise training ameliorated the treatment-induced intramuscular inflammation. Moreover, exercise has been suggested to convert Kyn to the neuroprotective metabolite, kynurenic acid (KA), but despite marked functional and muscular exercise-mediated adaptations, we did not observe any enhancement of KA production and related enzyme expression in the muscles of GEJ cancer patients. Exercise training reduced symptoms of depression in patients with GEJ cancer, and this effect was associated with an exercise-dependent attenuation of the inflammation-induced conversion of Kyn to neurotoxic metabolites.
运动可能改善癌症患者的抑郁症状，但这种保护作用的分子机制尚不清楚。在这里，我们旨在探讨运动与犬尿氨酸（Kyn）代谢和炎症之间的联系，这些联系在接受可手术胃食管交界处（GEJ）癌症患者中得到了改善，这些患者的抑郁评分在运动训练后显著降低。50 名 GEJ 癌症患者被分配到 12 周的监督训练中，每周两次，包括基于间歇的有氧运动和阻力训练，或标准护理。通过 HADS 评估抑郁评分，采集血液样本和肌肉活检，以在干预过程中确定 Kyn 代谢和炎症。运动组的抑郁评分降低了 -1.3 分（<0.01），而对照组没有变化。血浆 3-羟基犬尿氨酸（HK），一种可产生其他神经毒性代谢物的 Kyn 代谢物，在对照组中增加了 48%（<0.001），而运动训练则减弱了这种积累。HK 的产生是由炎症引起的，虽然我们没有观察到系统促炎细胞因子的差异，但运动训练改善了治疗引起的肌肉内炎症。此外，运动被认为可以将 Kyn 转化为神经保护代谢物，犬尿氨酸酸（KA），但尽管有明显的功能和肌肉运动介导的适应性，我们没有观察到 GEJ 癌症患者肌肉中 KA 产生和相关酶表达的增强。运动训练减轻了 GEJ 癌症患者的抑郁症状，这种效果与运动依赖性减轻炎症诱导的 Kyn 向神经毒性代谢物的转化有关。
