Integrative Muscle Biology Laboratory, Exercise Science Department, University of South Carolina, Columbia, SC, USA.
J Cachexia Sarcopenia Muscle. 2012 Jun;3(2):117-37. doi: 10.1007/s13539-011-0047-1. Epub 2011 Nov 30.
Cachexia involves unintentional body weight loss including diminished muscle and adipose tissue mass and is associated with an underlying disease. Systemic overexpression of IL-6 accelerates cachexia in the Apc(Min/+) mouse, but does not induce wasting in control C57BL/6 mice. With many chronic diseases, chronic inflammation and metabolic dysfunction can be improved with moderate exercise. A direct effect of regular moderate exercise on the prevention of IL-6-induced cachexia in the Apc(Min/+) mouse has not been investigated. The purpose of this study was to assess the effects of exercise on the development of cachexia in the Apc(Min/+) mouse.
Mice were randomly assigned to moderate treadmill exercise (18 m/min, 1 h, 6 days/week, 5% grade) or cage control (CC) groups from 6 to 14 weeks of age. At 12 weeks of age, mice were electroporated with either IL-6-containing or control plasmid into the quadriceps muscle. Mice were killed after 2 weeks of systemic IL-6 overexpression or control treatment.
IL-6 overexpression induced an 8% loss in body weight in CC mice, which was significantly attenuated by exercise. IL-6 overexpression in CC mice increased fasting insulin and triglyceride levels, which were normalized by exercise, and associated with increased oxidative capacity, an induction of AKT signaling, and a repression of AMPK signaling in muscle. These exercise-induced changes occurred despite elevated inflammatory signaling in skeletal muscle.
We conclude that moderate-intensity exercise can attenuate IL-6-dependent cachexia in Apc(Min/+) mice, independent of changes in IL-6 concentration and muscle inflammatory signaling. The exercise effect was associated with improved insulin sensitivity and improved energy status in the muscle.
恶病质涉及非故意的体重减轻，包括肌肉和脂肪组织质量的减少，并且与潜在疾病有关。IL-6 的全身过表达会加速 Apc(Min/+)小鼠的恶病质，但不会诱导对照 C57BL/6 小鼠消瘦。对于许多慢性疾病，慢性炎症和代谢功能障碍可以通过适度运动得到改善。定期适度运动对预防 Apc(Min/+)小鼠中 IL-6 诱导的恶病质的直接影响尚未得到研究。本研究旨在评估运动对 Apc(Min/+)小鼠恶病质发展的影响。
从 6 至 14 周龄起，将小鼠随机分配到适度跑步机运动（18 m/min，1 h，每周 6 天，5%坡度）或笼对照（CC）组。在 12 周龄时，将含有 IL-6 的质粒或对照质粒用电穿孔转染到股四头肌中。在全身 IL-6 过表达或对照处理 2 周后处死小鼠。
IL-6 过表达导致 CC 小鼠体重减轻 8%，运动显著减轻了这种体重减轻。CC 小鼠的 IL-6 过表达增加了空腹胰岛素和甘油三酯水平，运动使其正常化，并与肌肉中氧化能力增加、AKT 信号转导诱导和 AMPK 信号转导抑制有关。尽管骨骼肌中存在炎症信号升高，但仍发生了这些运动引起的变化。
我们得出结论，适度强度的运动可以减轻 Apc(Min/+)小鼠中依赖于 IL-6 的恶病质，而与肌肉中 IL-6 浓度和炎症信号的变化无关。运动的效果与改善肌肉胰岛素敏感性和改善能量状态有关。
