Adenovirus 36 Attenuates Weight Loss from Exercise but Improves Glycemic Control by Increasing Mitochondrial Activity in the Liver

Human adenovirus type 36 (Ad36) as an obesity agent induces adiposity by increasing glucose uptake and promoting chronic inflammation in fat tissues; in contrast, exercise reduces total body fat and inflammation. Our objective was to determine the association between Ad36 and the effects of exercise on inflammation and glycemic control. In the human trials (n = 54), Korean children (aged 12–14 years) exercised for 60 min on three occasions each week for 2 months. We compared the body mass index (BMI) Z-scores before and after exercise. C57BL/6 mice were infected with Ad36 and Ad2 as a control, and these mice exercised for 12 weeks postinfection. After the exercise period, we determined the serum parameters and assessed the presence of inflammation and the mitochondrial function in the organs. Ad36-seropositive children who were subjected to a supervised exercise regimen had high BMI Z-scores whereas Ad36-seronegative children had lower scores. Similarly, Ad36-infected mice were resistant to weight loss and exhibited chronic inflammation of their adipose tissues despite frequent exercise. However, Ad36 combined with exercise reduced the levels of serum glucose, nonesterified fatty acids, total cholesterol, and insulin in virus-infected mice. Interestingly, virus infection increased the mitochondrial function in the liver, as demonstrated by the numbers of mitochondria, cytochrome c oxidase activity, and transcription of key mitochondrial genes. Therefore Ad36 counteracts the weight-loss effect of exercise and maintains the chronic inflammatory state, but glycemic control is improved by exercise synergistically because of increased mitochondrial activity in the liver.36型人类腺病毒（Ad36，Human adenovirus type 36）作为一种致肥胖病毒，可通过增强葡萄糖摄取、促进脂肪组织慢性炎症诱导肥胖；与之相反，运动能够降低机体总脂肪量并减轻炎症反应。本研究旨在探讨Ad36与运动对炎症及血糖调控的影响之间的关联。在人体试验中（n=54），研究对象为12~14岁的韩国儿童，受试者每周进行3次、每次60分钟的运动，持续2个月。我们对比了受试者运动前后的体重指数（BMI，Body Mass Index）Z评分。以Ad2作为对照，对C57BL/6小鼠感染Ad36，随后在感染后让小鼠进行为期12周的运动干预。运动干预结束后，我们检测了小鼠的血清学指标，并评估了各器官的炎症状态与线粒体功能。接受监督式运动方案的Ad36血清学阳性儿童，其BMI Z评分较高；而Ad36血清学阴性儿童的BMI Z评分则相对较低。与之类似，尽管进行了规律运动，接种Ad36的小鼠仍难以出现体重下降，并表现出脂肪组织慢性炎症。然而，Ad36感染联合运动干预可降低病毒感染小鼠的血清葡萄糖、非酯化脂肪酸（Nonesterified Fatty Acids）、总胆固醇与胰岛素水平。值得注意的是，病毒感染可增强肝脏的线粒体功能，这一点可通过线粒体数量、细胞色素c氧化酶（Cytochrome c Oxidase）活性以及关键线粒体基因的转录水平得到验证。综上，Ad36可抵消运动的减重效果并维持慢性炎症状态，但由于肝脏线粒体活性提升，运动可协同改善血糖调控。