Division of General Medical Rehabilitation, Geneva University Hospitals, Geneva, Switzerland.
Nutrition. 2011 Feb;27(2):138-43. doi: 10.1016/j.nut.2010.07.009. Epub 2010 Dec 9.
In patients with chronic obstructive pulmonary disease (COPD), malnutrition and limited physical activity are very common and contribute to disease prognosis, whereas a balance between caloric intake and exercise allows body weight stability and muscle mass preservation. The goal of this review is to analyze the implications of chronic hypoxia on three key elements involved in energy homeostasis and its role in COPD cachexia. The first one is energy intake. Body weight loss, often observed in patients with COPD, is related to lack of appetite. Inflammatory cytokines are known to be involved in anorexia and to be correlated to arterial partial pressure of oxygen. Recent studies in animals have investigated the role of hypoxia in peptides involved in food consumption such as leptin, ghrelin, and adenosine monophosphate activated protein kinase. The second element is muscle function, which is strongly related to energy use. In COPD, muscle atrophy and muscle fiber shift to the glycolytic type might be an adaptation to chronic hypoxia to preserve the muscle from oxidative stress. Muscle atrophy could be the result of a marked activation of the ubiquitin-proteasome pathway as found in muscle of patients with COPD. Hypoxia, via hypoxia inducible factor-1, is implicated in mitochondrial biogenesis and autophagy. Third, hormonal control of energy balance seems to be affected in patients with COPD. Insulin resistance has been described in this group of patients as well as a sort of "growth hormone resistance." Hypoxia, by hypoxia inducible factor-1, accelerates the degradation of tri-iodothyronine and thyroxine, decreasing cellular oxygen consumption, suggesting an adaptive mechanism rather than a primary cause of COPD cachexia. COPD rehabilitation aimed at maintaining function and quality of life needs to address body weight stabilization and, in particular, muscle mass preservation.
在慢性阻塞性肺疾病（COPD）患者中，营养不良和体力活动受限非常常见，这会影响疾病的预后，而热量摄入和运动之间的平衡则可以维持体重稳定和保持肌肉量。本综述的目的是分析慢性缺氧对能量平衡的三个关键因素的影响，以及其在 COPD 恶病质中的作用。第一个因素是能量摄入。COPD 患者常出现体重下降，这与食欲下降有关。已知炎症细胞因子与厌食症有关，并且与动脉血氧分压相关。最近在动物中的研究调查了缺氧在参与食物摄入的肽（如瘦素、胃饥饿素和单磷酸腺苷激活蛋白激酶）中的作用。第二个因素是肌肉功能，它与能量的使用密切相关。在 COPD 中，肌肉萎缩和肌肉纤维向糖酵解型的转变可能是对慢性缺氧的一种适应，以保护肌肉免受氧化应激。肌肉萎缩可能是由于泛素-蛋白酶体途径的显著激活所致，这种激活在 COPD 患者的肌肉中已被发现。缺氧通过缺氧诱导因子-1 参与线粒体生物发生和自噬。第三，能量平衡的激素控制似乎在 COPD 患者中受到影响。该组患者中存在胰岛素抵抗以及某种“生长激素抵抗”。缺氧通过缺氧诱导因子-1 加速三碘甲状腺原氨酸和甲状腺素的降解，降低细胞的耗氧量，这表明这是一种适应性机制，而不是 COPD 恶病质的主要原因。旨在维持功能和生活质量的 COPD 康复需要解决体重稳定的问题，特别是要保持肌肉量。
