Disturbances in leptin metabolism are related to energy imbalance during acute exacerbations of chronic obstructive pulmonary disease
Disturbances in leptin metabolism are related to energy imbalance during acute exacerbations of chronic obstructive pulmonary disease
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DOI：
10.1164/ajrccm.162.4.9912016
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发表时间：
2000-10-01
影响因子：
24.7
通讯作者：
Schols, AMWJ
中科院分区：
文献类型：
--
作者：
Creutzberg, EC;Wouters, EFM;Schols, AMWJ
以前我们报道了慢性阻塞性肺疾病（COPD）患者在急性疾病加重期间的能量平衡受损，但关于其潜在机制的数据有限。实验和临床研究支持瘦素参与体重和能量平衡稳态的假设。本研究的目的是调查重度COPD患者在急性加重住院的前7天内与瘦素和可溶性肿瘤坏死因子（TNF）受体（sTNF-R）55和75、血糖和血清胰岛素相关的能量平衡过程（n = 17，11例男性，平均年龄[SD] 66 [10]岁，FEV 1 36 [12] %预测值）。对于实验室参数的参考值，从23名（16名男性）健康老年受试者中采集血液。入院时，饮食摄入/静息能量消耗（REE）比值严重降低（1.28 [0.57]），但逐渐恢复至第7天（1.65 [0.45]，p = 0.005 vs第1天）。入院时血糖和胰岛素浓度升高，但第7天仅血糖降低。sTNF-R与健康受试者没有差异，也没有变化。与健康受试者相比，第1天血浆瘦素（根据脂肪质量校正，表示为体重百分比（%FM））升高（1.82 [3.85] vs 0.32 [0.72] ng%/ml，p = 0.008），但直到第7天显著降低（1.46 [3.77] ng%/ml，p = 0.015 vs第1天）。在第7天，sTNF-R55独立于%FM，与瘦素的自然对数（LN）（r = 0.65，p = 0.041）和血浆葡萄糖（r = 0.81，p = 0.015）相关。此外，饮食摄入/PEE比率不仅与LN瘦素（-0.74，p = 0.037）负相关，而且与第7天的sTNF-R55（r =-0.93，p = 0.001）负相关。总之，在COPD急性加重期间观察到能量平衡的暂时性紊乱，这与瘦素浓度增加以及全身炎症反应有关。有证据表明，升高的瘦素浓度反过来又受到全身炎症反应的控制，并且据推测，受到高剂量全身性糖皮质激素治疗的控制。
Previously we reported an impaired energy balance in patients with chronic obstructive pulmonary disease (COPD) during an acute disease exacerbation, but limited data are available on the underlying mechanisms. Experimental and clinical research supports the hypothesis of involvement of the hormone leptin in body weight and energy balance homeostasis. The aim of this study was to investigate the course of the energy balance in relation to leptin and the soluble tumor necrosis factor (TNF) receptors (sTNF-R) 55 and 75, plasma glucose, and serum insulin in patients with severe COPD during the first 7 d of hospitalization for an acute exacerbation (n = 17, 11 men, age mean [SD] 66 [10] yr, FEV1 36 [12] %pred). For reference values of the laboratory parameters, blood was collected from 23 (16 men) healthy, elderly subjects. On admission, the dietary intake/resting energy expenditure (REE) ratio was severely depressed (1.28 [0.57]), but gradually restored until Day 7 (1.65 [0.45], p = 0.005 versus Day 1). Glucose and insulin concentrations were elevated on admission, but on Day 7 only plasma glucose was decreased. The sTNF-Rs were not different from healthy subjects and did not change. Plasma leptin, adjusted for fat mass expressed as percentage of body weight (%FM), was elevated on Day 1 compared with healthy subjects (1.82 [3.85] versus 0.32 [0.72] ng%/ml, p = 0.008), but decreased significantly until Day 7 (1.46 [3.77] ng%/ml, p = 0.015 versus Day 1). On Day 7, sTNF-R55 was, independently of %FM, correlated with the natural logarithm (LN) of leptin (r = 0.65, p = 0.041) and with plasma glucose (r = 0.81, p = 0.015). In addition, the dietary intake/PEE ratio was not only inversely related with LN leptin (-0.74, p = 0.037), but also with sTNF-R55 (r = -0.93, p = 0.001) on day seven. In conclusion, temporary disturbances in the energy balance were seen during an acute exacerbation of COPD, related to increased leptin concentrations as well as to the systemic inflammatory response. Evidence was found that the elevated leptin concentrations were in turn under control of the systemic inflammatory response, and, presumably, the high-dose systemic glucocorticosteroid treatment.