Bódis Kálmán, Breuer Saida, Crepzia-Pevzner Assja, Zaharia Oana-Patricia, Schön Martin, Saatmann Nina, Altenhofen Delsi, Springer Christian, Szendroedi Julia, Wagner Robert, Al-Hasani Hadi, Roden Michael, Pesta Dominik, Chadt Alexandra
Department of Endocrinology and Diabetology, Medical Faculty and University Hospital, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany.
Diabetes Obes Metab. 2024 Jan;26(1):339-350. doi: 10.1111/dom.15322. Epub 2023 Oct 23.
Exercise training induces white adipose tissue (WAT) beiging and improves glucose homeostasis and mitochondrial function in rodents. This could be relevant for type 2 diabetes in humans, but the effect of physical fitness on beiging of subcutaneous WAT (scWAT) remains unclear. This translational study investigates if beiging of scWAT associates with physical fitness in healthy humans and recent-onset type 2 diabetes and if a voluntary running wheel intervention is sufficient to induce beiging in mice.
Gene expression levels of established beiging markers were measured in scWAT biopsies of humans with (n = 28) or without type 2 diabetes (n = 28), stratified by spiroergometry into low (L-FIT; n = 14 each) and high physical fitness (H-FIT; n = 14 each). High-fat diet-fed FVB/N mice underwent voluntary wheel running, treadmill training or no training (n = 8 each group). Following the training intervention, mitochondrial respiration and content of scWAT were assessed by high-resolution respirometry and citrate synthase activity, respectively.
Secreted CD137 antigen (Tnfrsf9/Cd137) expression was three-fold higher in glucose-tolerant H-FIT than in L-FIT, but not different between H-FIT and L-FIT with type 2 diabetes. In mice, both training modalities increased Cd137 expression and enhanced mitochondrial content without changing respiration in scWAT. Treadmill but not voluntary wheel running led to improved whole-body insulin sensitivity.
Higher physical fitness and different exercise interventions associated with higher gene expression levels of the beiging marker CD137 in healthy humans and mice on a high-fat diet. Humans with recent-onset type 2 diabetes show an impaired adipose tissue-specific response to physical activity.
运动训练可诱导啮齿动物白色脂肪组织（WAT）米色化，并改善葡萄糖稳态和线粒体功能。这可能与人类2型糖尿病有关，但体能对皮下WAT（scWAT）米色化的影响尚不清楚。这项转化研究调查了scWAT的米色化是否与健康人和近期发病的2型糖尿病患者的体能相关，以及自愿跑步轮干预是否足以诱导小鼠米色化。
在有（n = 28）或无2型糖尿病（n = 28）的人类scWAT活检组织中测量已确定的米色化标志物的基因表达水平，通过运动心肺功能测试将其分为低体能（L-FIT；每组n = 14）和高体能（H-FIT；每组n = 14）。高脂饮食喂养的FVB/N小鼠接受自愿跑步轮训练、跑步机训练或不训练（每组n = 8）。训练干预后，分别通过高分辨率呼吸测定法和柠檬酸合酶活性评估scWAT的线粒体呼吸和含量。
糖耐量正常的H-FIT组中分泌型CD137抗原（Tnfrsf9/Cd137）的表达比L-FIT组高3倍，但在2型糖尿病的H-FIT组和L-FIT组之间无差异。在小鼠中，两种训练方式均增加了Cd137的表达并提高了线粒体含量，但未改变scWAT的呼吸。跑步机训练而非自愿跑步轮训练可改善全身胰岛素敏感性。
在高脂饮食的健康人和小鼠中，较高的体能和不同的运动干预与米色化标志物CD137的较高基因表达水平相关。近期发病的2型糖尿病患者的脂肪组织对身体活动的特异性反应受损。
