Division of Kinesiology and Health, University of Wyoming, Laramie, Wyoming, USA.
Wyoming WWAMI Medical Education, Laramie, Wyoming, USA.
High Alt Med Biol. 2022 Sep;23(3):215-222. doi: 10.1089/ham.2022.0015. Epub 2022 Jun 2.
Fullerton, Zackery S., Benjamin D. McNair, Nicholas A. Marcello, Emily E. Schmitt, and Danielle R. Bruns. Exposure to high altitude promotes loss of muscle mass that is not rescued by metformin. 23:215-222, 2022. Exposure to high altitude (HA) causes muscle atrophy. Few therapeutic interventions attenuate muscle atrophy; however, the diabetic drug, metformin (Met), has been suggested as a potential therapeutic to preserve muscle mass with aging and obesity-related atrophy. The purpose of the present study was to test the hypothesis that HA would induce muscle atrophy that could be attenuated by Met. C57Bl6 male and female mice were exposed to simulated HA (∼5,200 m) for 4 weeks, while control (Con) mice remained at resident altitude (∼2,180 m). Met was administered in drinking water at 200 mg/(kg·day). We assessed muscle mass, myocyte cell size, muscle and body composition, and expression of molecular mediators of atrophy. Mice exposed to HA were leaner and had a smaller hind limb complex (HLC) mass than Con mice. Loss of HLC mass and myocyte size were not attenuated by Met. Molecular markers for muscle atrophy were activated at HA in a sex-dependent manner. While the atrophic regulator, atrogin, was unchanged at HA or with Met, myostatin expression was upregulated at HA. In female mice, Met further stimulated myostatin expression. Although HA exposure resulted in loss of muscle mass, particularly in male mice, Met did not attenuate muscle atrophy. Identification of other interventions to preserve muscle mass during ascent to HA is warranted.
富勒顿，扎克里 S.，本杰明 D. 麦克奈尔，尼古拉斯 A. 马塞洛，艾米丽 E. 施密特和丹妮尔 R. 布鲁恩。高海拔暴露会导致肌肉质量减少，而二甲双胍无法挽救这种减少。23：215-222，2022。高海拔暴露（HA）会导致肌肉萎缩。很少有治疗干预措施可以减轻肌肉萎缩；然而，糖尿病药物二甲双胍（Met）已被提议作为一种潜在的治疗方法，以防止与衰老和肥胖相关的肌肉萎缩。本研究的目的是测试 HA 是否会引起肌肉萎缩，而 Met 可以减轻这种萎缩的假设。雄性和雌性 C57Bl6 小鼠分别暴露于模拟 HA（约 5200 米）4 周，而对照（Con）小鼠则保持在居住地海拔（约 2180 米）。Met 通过饮用水给药，剂量为 200mg/（kg·天）。我们评估了肌肉质量、肌细胞大小、肌肉和身体成分以及萎缩相关分子介质的表达。暴露于 HA 的小鼠比 Con 小鼠更瘦，后腿复合体（HLC）质量更小。Met 不能减轻 HLC 质量和肌细胞大小的减少。以性别依赖的方式，肌肉萎缩的分子标志物在 HA 处被激活。虽然在 HA 或 Met 处，萎缩调节因子 atrogin 没有变化，但肌肉生长抑制素表达上调。在雌性小鼠中，Met 进一步刺激肌肉生长抑制素表达。尽管 HA 暴露导致肌肉质量减少，特别是在雄性小鼠中，但 Met 并不能减轻肌肉萎缩。需要确定其他干预措施来维持 HA 上升期间的肌肉质量。
