Toth Michael J, Callahan Damien M, Miller Mark S, Tourville Timothy W, Hackett Sarah B, Couch Marion E, Dittus Kim
Department of Medicine, University of Vermont, College of Medicine, Burlington, VT, USA; Department of Molecular Physiology and Biophysics, University of Vermont, College of Medicine, Burlington, VT, USA; Department of Orthopaedics and Rehabilitation, University of Vermont, College of Medicine, Burlington, VT, USA.
Department of Medicine, University of Vermont, College of Medicine, Burlington, VT, USA.
Clin Nutr. 2016 Dec;35(6):1359-1365. doi: 10.1016/j.clnu.2016.02.016. Epub 2016 Mar 8.
BACKGROUND & AIMS: Cancer patients frequently experience weight loss, with negative consequences for functionality and prognosis. The extent to which muscle atrophy contributes to weight loss, however, is not clear, as few studies have directly measured muscle fiber morphology in cancer patients.
Whole body and regional tissue composition were measured, along with the cross-sectional area (CSA) and fiber type of mechanically-isolated, single muscle fibers, in 19 cancer patients (8 with a history of weight loss, 11 weight-stable) and 15 non-diseased controls.
Whole body fat mass was reduced in cancer patients with a history of weight loss, but no differences in whole body or leg fat-free mass were apparent. In contrast, reductions (∼20%) in single muscle fiber CSA were found in both slow-twitch, myosin heavy chain (MHC) I and fast-twitch, MHC IIA fibers in both weight-stable patients and those with a history of weight loss. Fiber type distribution showed a shift towards a fast-twitch phenotype compared to controls, which may preserve muscle function in cancer patients despite atrophy, as positive relationships were found between the fractions of hybrid MHC IIAX and I/IIA fibers and 6-min walk performance.
Our results suggest that, although not apparent from whole body or regional measurements, cancer is associated with reduced skeletal muscle fiber size independent of weight loss history and a shift towards fast-twitch fibers, phenotypes that resemble adaptations to muscle disuse.
癌症患者经常出现体重减轻,这对身体功能和预后会产生负面影响。然而,肌肉萎缩对体重减轻的影响程度尚不清楚,因为很少有研究直接测量癌症患者的肌纤维形态。
对19名癌症患者(8名有体重减轻史,11名体重稳定)和15名非患病对照者测量了全身和局部组织成分,以及机械分离的单根肌纤维的横截面积(CSA)和纤维类型。
有体重减轻史的癌症患者全身脂肪量减少,但全身或腿部去脂体重无明显差异。相比之下,在体重稳定的患者和有体重减轻史的患者中,慢肌球蛋白重链(MHC)I型和快肌MHC IIA型单根肌纤维的CSA均减少(约20%)。与对照组相比,纤维类型分布向快肌表型转变,这可能使癌症患者尽管存在萎缩仍能保持肌肉功能,因为混合MHC IIAX和I/IIA型纤维的比例与6分钟步行表现之间存在正相关。
我们的结果表明,尽管从全身或局部测量中不明显,但癌症与骨骼肌纤维尺寸减小有关,与体重减轻史无关,且向快肌纤维转变,这些表型类似于对肌肉废用的适应性变化。