Elevated Circulating Plasma Adiponectin in Underweight Patients With COPD

doi:10.1378/chest.07-0227

Chest

Volume 132, Issue 1, July 2007, Pages 135-140

https://doi.org/10.1378/chest.07-0227 Get rights and content

Background:

Adiponectin is an adipose tissue-derived specific protein that has antiinflammatory as well as antiatherosclerotic effects. In the United States, many patients with COPD are obese and die of cardiovascular diseases. However, in Japan, patients with COPD are frequently cachexic and die of respiratory failure. This study was designed to investigate the role of adiponectin in these differences in characteristics of COPD.

Methods:

We enrolled normal-weight and underweight male patients with COPD (n = 31; age, 71 ± 1 years; body mass index [BMI], 20.1 ± 0.6 kg/m²) and age-matched, healthy, male, control subjects (n = 12). The adiponectin levels were measured by enzyme-linked immunosorbent assay. Correlation of adiponectin levels with pulmonary function and serum levels of proinflammatory cytokines (tumor necrosis factor [TNF]-α and interleukin-6) were estimated.

Results:

Adiponectin levels in patients with COPD were significantly higher than those in control subjects (p<0.01) and inversely correlated with BMI (r = − 0.55, p<0.01). Even in the normal-weight patients with COPD, adiponectin levels were significantly higher than those in control subjects (p<0.01). Adiponectin levels in patients with COPD significantly correlated with percentage of predicted residual volume (r = 0.40, p<0.05). In patients with TNF-α levels > 5 pg/mL, there was a significant correlation between plasma adiponectin and serum TNF-α levels (r = 0.68, p<0.05).

Conclusions:

Plasma adiponectin levels in patients with COPD were elevated and correlated with body weight loss, hyperinflation, and systemic inflammation. Increased adiponectin may reduce cardiovascular events in underweight patients with COPD.

Section snippets

Subjects

We studied 31 consecutive, consenting, male patients with COPD who met our entry criteria (mean age, 71 years; range, 56 to 83 years). Only men were enrolled in this study because visceral fat mass varies according to gender. COPD was diagnosed according to the Global Initiative for Chronic Obstructive Lung Disease criteria.¹⁰ All patients were clinically stable at the time of evaluation. This study included age-matched, male, control subjects who had normal pulmonary function. The

Characteristics of Subjects

Clinical characteristics of normal-weight and underweight patients with COPD and healthy control subjects are summarized in Table 1. The residual volume (RV) of underweight patients was higher than that of normal-weight patients. However, there were no significant differences in FEV₁, Pao₂, and Paco₂ between the two groups in COPD. Of the 31 enrolled patients, 27 patients whose percentage of diffusion capacity of the lung for carbon monoxide (Dlco) ranged from 4.3 to 59.9% and whose RV/total

Discussion

We showed that plasma adiponectin levels in normal-weight and underweight patients with COPD were remarkably elevated and that the elevated adiponectin level was associated with several pathophysiologic findings in COPD. BMI inversely correlated with plasma adiponectin levels in patients with COPD. It was previously demonstrated that in obese patients, adiponectin levels were significantly decreased and inversely correlated with both body weight and fat mass. In patients with anorexia nervosa¹²

ACKNOWLEDGMENT

The authors are indebted to Professor J. Patrick Barron of the International Medical Communications Center of Tokyo Medical University for his review of this article.

References (34)

Y Arita et al.
Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity
Biochem Biophys Res Commun
(1999)
DM Mannino et al.
Global Initiative on Obstructive Lung Disease (GOLD) classification of lung disease and mortality: findings from the Atherosclerosis Risk in Communities (ARIC) study
Respir Med
(2006)
DD Sin et al.
The relationship between reduced lung function and cardiovascular mortality: a population-based study and a systematic review of the literature
Chest
(2005)
Q Zeng et al.
Effects of exercise on adiponectin and adiponectin receptor levels in rats
Life Sci
(2007)
S Guerra et al.
The relation of body mass index to asthma, chronic bronchitis, and emphysema
Chest
(2002)
Y Kitaguchi et al.
Characteristics of COPD phenotypes classified according to the findings of HRCT
Respir Med
(2006)
Y Matsuzawa et al.
Adiponectin and metabolic syndrome
Arterioscler Thromb Vasc Biol
(2004)
N Stefan et al.
Plasma adiponectin concentration is associated with skeletal muscle insulin receptor tyrosine phosphorylation, and low plasma concentration precedes a decrease in whole-body insulin sensitivity in humans
Diabetes
(2002)
M Kumada et al.
Association of hypoadiponectinemia with coronary artery disease in men
Arterioscler Thromb Vasc Biol
(2003)
NR Anthonisen et al.
Hospitalizations and mortality in the Lung Health Study
Am J Respir Crit Care Med
(2002)

C Fuhrman et al.

Chronic obstructive pulmonary disease deaths in France, 1979–2002: a multiple-cause analysis

Thorax

(2006)

K Miyamoto et al.

Gender effect on prognosis of patients receiving long-term home oxygen therapy: the Respiratory Failure Research Group in Japan

Am J Respir Crit Care Med

(1995)

Global Initiative for Chronic Obstructive Lung Disease

Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease, April 2001 (update 2004)

E Berglund et al.

Spirometric studies in normal subjects: I. Forced expirograms in subjects between 7 and 70 years of age

Acta Med Scand

(1963)

N Pannacciulli et al.

Anorexia nervosa is characterized by increased adiponectin plasma levels and reduced nonoxidative glucose metabolism

J Clin Endocrinol Metab

(2003)

I Wolf et al.

Adiponectin, ghrelin, and leptin in cancer cachexia in breast and colon cancer patients

Cancer

(2006)

WD Pitcher et al.

Oxygen cost of increasing tidal volume and diaphragm flattening in obstructive pulmonary disease

J Appl Physiol

(1993)

Cited by (106)

Differential impacts between fat mass index and fat-free mass index on patients with COPD
2023, Respiratory Medicine
Differences in the clinical impacts of fat mass index (FMI) and fat-free mass index (FFMI) remain unclear in patients with chronic obstructive pulmonary disease (COPD). We hypothesized that FMI and FFMI have different impacts on 1) emphysema and 2) pulmonary function and health-related quality of life of COPD patients.
Patients with COPD (n = 228), enrolled in a multicenter prospective 3-year cohort were classified into four groups based on baseline median FMI and FFMI values. Emphysema assessed as the ratio of low attenuation area to total lung volume (LAA%) on computed tomography, pulmonary function, and health-related quality of life assessed using the St. George's Respiratory Questionnaire (SGRQ) were compared.
The four groups had statistically significant differences in LAA%, pulmonary function, and SGRQ scores. The Low FMI Low FFMI group exhibited the highest LAA%, lowest pulmonary function, and worst SGRQ scores among the four groups. In addition, these differences were consistent over 3 years. Multivariate analysis showed that low FMI was associated with high LAA%, low inspiratory capacity/total lung capacity (IC/TLC), and carbon monoxide transfer coefficient (K_CO). In contrast, low FFMI was associated with these factors as well as worse SGRQ scores.
FMI and FFMI have different effects on the clinical manifestations of COPD. Both low fat and muscle mass contributed to severe emphysema, whereas only low muscle mass contributed to worse health-related quality of life in patients with COPD.
Body mass index as a predictor of mortality in bronchiectasis: A nationwide population-based study
2021, Respiratory Medicine
Citation Excerpt :
However, the reason can be speculated from COPD studies because bronchiectasis is common in patients with COPD, and both diseases share many clinical and etiological features[17]. In COPD, several reasons for the association between a low BMI and increased mortality have been suggested, including a low fat-free mass index (fat-free mass/weight2) and diaphragmatic muscle weakness[18], early emphysema in chronic malnutrition[19], and increased systemic inflammation in underweight patients[20,21]. The risk factors for poor outcomes in bronchiectasis are still unknown and rank high in research priorities[22].
The prognosis of bronchiectasis is not well known. The purpose of this study was to evaluate the association between body mass index (BMI) and mortality in bronchiectasis using a large nationwide population-based cohort.
Using the National Health Insurance Service-Health Screening Cohort in Korea, individuals with bronchiectasis were identified from 2004 to 2006 and monitored for up to 10 years. Mortality in bronchiectasis was analyzed based on a BMI score <18.5 kg/m² (underweight), 1.85–22.9 kg/m² (normal weight), 23.0–24.9 kg/m² (overweight), and >25.0 kg/m² (obese).
A total of 2769 individuals with bronchiectasis were included. The underweight, normal weight, overweight, and obese accounted for 5.1%, 40.4%, 25.4%, and 29.3% of all patients with bronchiectasis, respectively. Compared to normal weight, underweight in bronchiectasis was associated with increased all-cause mortality (hazard ratio [HR] = 2.60; 95% confidence interval [CI] = 1.92–3.54), while obese was associated with decreased all-cause mortality (HR = 0.71; 95% CI = 0.55–0.93). This relationship between BMI and mortality was more prominent in respiratory disease-related mortality.
BMI is a predictor of mortality in bronchiectasis. Underweight is associated with increased mortality among individuals with bronchiectasis while obese is associated with decreased mortality.
Contentious role of ‘Good Adiponectin’ in pulmonary and cardiovascular diseases: Is adiponectin directed therapy a boon or a bane?
2020, Biochimie
Citation Excerpt :
Chronic heart disease (CHD) in obese [26,27], chronic obstructive pulmonary disease (COPD) [74], acute heart failure (AHF) [26,27] chronic heart failure (CHF) and acute coronary syndrome (ACS) [65] are some of the cardiovascular and pulmonary anomalies which are exaggerated by up-regulated APN. Additionally, APN is also reported to be up-regulated in aging patients, who are at high risk of cardiovascular disease (CVD) [23] as well as in normal/underweight cachectic COPD patients [24]. APN receptor AdipoR2 is found to be upregulated in epithelial cells of obese asthma patients which tend to decrease gradually followed by down-regulation of T-cadherin [25].
After two decades of its discovery, numerous facts of adiponectin (APN) biology has been uncovered, yet, APN remains an elusive adipokine. Findings from clinical studies and animal models established APN’s ameliorative role in cardiovascular disease (CVD) and pulmonary disease (PD) but the same condition is prognostic for mortality in the same set of patients which cornered APN towards a dubious state. A repertoire of mechanisms associated with the positive association of APN in both lean/cachectic or obese CVD and PD patients from past publications are evaluated. Newer pharmacological agent may be explored to regulate elevated blood APN concentration in COPD or CHF patients whereas administration of recombinant APN as well as growth hormone may augment blood APN concentration in obese subjects associated with low blood and intracellular APN concentration. However, some APN directed therapy in clinical as well as in pre-clinical setup has pronounced some contentious effects. After reviewing the mechanisms of the contentious role of APN functioning in pathologic conditions of CVD and PD in both lean and obese conditions, the authors came to conclusion that APN directed therapy may be utilized with caution keeping in mind the different age group, sex and the different CVD as well as pulmonary diseases they are suffering from.
Impact of reduced pulmonary function in the Japanese general population: Lessons from the Yamagata-Takahata study
2019, Respiratory Investigation
Regional epidemiological studies for respiratory diseases have been rarely performed in Japan, because spirometry is not regularly conducted in the standard annual health checks. The Yamagata-Takahata Study is an epidemiological study utilizing regional characteristics based on the 21st Century Centers of Excellence (COE) Program and the Global COE Program. Spirometric examination and other specific measurements via blood sampling were performed for the study participants in annual health check-ups held in Takahata, a town in Yamagata Prefecture. The Yamagata-Takahata Study revealed the impact of cigarette smoking habit on pulmonary function, the impact of reduced pulmonary function on mortality, and the situation regarding COPD comorbidities in Japan. Additionally, the study identified biomarkers of decline in pulmonary function among active smokers, and the risk factors for respiratory mortality in Japan. In this review, we summarize the findings of the Yamagata-Takahata study regarding the association between lower pulmonary function and the clinical characteristics of a Japanese general population.
The burden of obesity in asthma and COPD: Role of adiponectin
2017, Pulmonary Pharmacology and Therapeutics
The influence of obesity on development, severity and prognosis of both asthma and COPD is attracting growing interest. The impact of obesity on the respiratory system ranges from structural modifications (decline of total lung capacity) to humoral alterations. Adipose tissue strongly contributes to the establishment of an inflammatory state being an important source of adipokines. Amongst adipokines, adiponectin is an important component of organ cross talk with adipose tissue exerting protective effects on a variety of pathophysiological processes. Adiponectin is secreted in serum where it abundantly circulates as complexes of different molecular weight. Adiponectin properties are mediated by specific receptors that are widely expressed with AdipoR1, AdipoR2, and T-cadherin being present on epithelial and endothelial pulmonary cells indicating a functional role on lung physiology.
In COPD, mild to moderate obesity has been shown to have protective effects on patient's survival, while a higher mortality rate has been observed in patients with low BMI. A specific cluster of obese patients has been identified; in this group, asthma features are particularly severe and difficult to treat. Better understanding of the molecular mechanisms at the base of cross talk among different tissues and organs will lead to identification of new targets for both diagnosis and treatment of asthma and COPD.
A reciprocal inhibitory relationship between adiponectin and mammalian cytosolic thioredoxin
2016, Science Bulletin
Thioredoxin is a redox protein while adiponectin is an adipokine. Their relationship has been less appreciated. Here we show that in serum of patients with acute exacerbations of chronic obstructive Pulmonary Disease, decreased activity of thioredoxin coexists with increased level of adiponectin as partial pressure of arterial oxygen decreases. From the results with adiponectin-knockout mice and in vitro experiments, we have found a reciprocal inhibitory relationship, by which adiponectin inhibits cytosolic thioredoxin (Trx1) expression, whereas serum Trx1 influences adiponectin multimerization. The association between extracellular Trx1 and adiponectin attenuates their functions. This relationship is dynamic, and correlated with a body’s physiological conditions.

View all citing articles on Scopus

This study was partly supported by a grant to the Respiratory Failure Research Group from the Japanese Ministry at Health Labor and Welfare.

The authors have no conflicts of interest to disclose.

View full text

Chest

ORIGINAL RESEARCHCOPDElevated Circulating Plasma Adiponectin in Underweight Patients With COPD

Background:

Methods:

Results:

Conclusions:

Section snippets

Subjects

Characteristics of Subjects

Discussion

ACKNOWLEDGMENT

Biochem Biophys Res Commun

Respir Med

Chest

Life Sci

Chest

Respir Med

Adiponectin and metabolic syndrome

Arterioscler Thromb Vasc Biol

Plasma adiponectin concentration is associated with skeletal muscle insulin receptor tyrosine phosphorylation, and low plasma concentration precedes a decrease in whole-body insulin sensitivity in humans

Diabetes

Association of hypoadiponectinemia with coronary artery disease in men

Arterioscler Thromb Vasc Biol

Hospitalizations and mortality in the Lung Health Study

Am J Respir Crit Care Med

Chronic obstructive pulmonary disease deaths in France, 1979–2002: a multiple-cause analysis

Thorax

Gender effect on prognosis of patients receiving long-term home oxygen therapy: the Respiratory Failure Research Group in Japan

Am J Respir Crit Care Med

Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease, April 2001 (update 2004)

Spirometric studies in normal subjects: I. Forced expirograms in subjects between 7 and 70 years of age

Acta Med Scand

Anorexia nervosa is characterized by increased adiponectin plasma levels and reduced nonoxidative glucose metabolism

J Clin Endocrinol Metab

Adiponectin, ghrelin, and leptin in cancer cachexia in breast and colon cancer patients

Cancer

Oxygen cost of increasing tidal volume and diaphragm flattening in obstructive pulmonary disease

J Appl Physiol

ORIGINAL RESEARCH
COPD
Elevated Circulating Plasma Adiponectin in Underweight Patients With COPD