Disturbances in Leptin Metabolism Are Related to Energy Imbalance during Acute Exacerbations of Chronic Obstructive Pulmonary Disease

Abstract

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, FEV(1) 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/REE 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.

Does leptin play a cytokine-like role within the airways of COPD patients?

“…The present study is the first investigating the leptin and leptin-receptor expression in the bronchial tissue of smokers with or without COPD. Previous findings have shown a relationship between leptin release in patients with COPD and wasting [16,17]. A pleiotropic role for leptin in mammalian physiology has been suggested, this being leptin-deficient mice characterised not only by obesity, but also by abnormalities in reproductive function, hormone levels, wound repair, bone structure, and immune function [13,27].…”

“…In some patients with COPD, plasmatic leptin levels are increased and this phenomenon is related to pro-inflammatory status and dietary intake [16]. Disturbances in leptin metabolism are related to energy imbalance during acute exacerbations of COPD [17]. COPD has been recognised as an inflammatory disease of the airways, however, it is increasingly being accepted that a link between airway and systemic inflammation may exist in COPD.…”

Nutritional assessment and therapy in COPD: a European Respiratory Society statement

“…Weight loss and wasting of muscle and bone tissue may be induced or accelerated during severe acute exacerbations requiring hospitalisation, due to convergence of different catabolic stimuli including malnutrition [58], physical inactivity [59], hypoxia, inflammation [60] and systemic glucocorticoids [61]. Moreover, this may be a time when energy intake may be compromised by practical difficulties in providing adequate nutrition due to breathlessness or other treatments such as noninvasive ventilation.…”

“…Furthermore, impaired responsiveness to signalling cues of muscle regeneration and protein synthesis may delay recovery and increase the risk for readmission [62]. In the acute phase of respiratory exacerbations, loss of appetite and reduced dietary intake are often experienced in concert with elevated systemic levels of the appetiteregulating hormone leptin and pro-inflammatory cytokines [58,60]. Next to nutritional risk screening and early intervention in primary care, hospitalisations could be considered an additional opportunity for detailed nutritional assessment and implementation of longer term nutritional management, as they represent a period of heightened ''nutritional risk'' that may, in itself, require intensive nutritional therapy [63].…”

Cachexia in chronic obstructive pulmonary disease: new insights and therapeutic perspective

“…In terms of caloric content, dietary intake was found to be normal compared with healthy controls, but inadequate for measured energy expenditure 118, 186, 187, 188. During severe acute exacerbations, the gap between energy intake and energy expenditure becomes even wider, which slowly decreases upon recovery 126, 189. To our knowledge, no human studies have systematically investigated the relation between dietary intake and disease severity or putative differences between emphysematous and non‐emphysematous patients.…”