Low-grade adipose tissue inflammation in patients with mild-to-moderate chronic obstructive pulmonary disease123

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Background: Low-grade systemic inflammation is common in chronic obstructive pulmonary disease (COPD), but its source remains unclear. Adipose tissue is a potent producer of inflammatory mediators and may contribute to systemic inflammation in COPD, possibly via hypoxia.

Objective: We studied the influence of COPD and exercise-induced oxygen desaturation on adipose tissue inflammation (ATI) and its contribution to systemic inflammation.

Design: Subcutaneous adipose tissue biopsies were investigated in 28 clinically stable COPD patients [forced expiratory volume in 1 s: 58 ± 16% predicted; BMI (in kg/m2): 24.9 ± 2.9] and 15 age-, sex-, and body composition–matched healthy control subjects. Fat mass was measured with dual-energy X-ray absorptiometry. Patients were prestratified by oxygen desaturation assessed by incremental cycle ergometry. The adipocyte size and adipose tissue expression of 19 inflammatory and hypoxia-related genes were measured, and adipose tissue macrophages (ATMs) were histologically quantified. Systemic inflammatory markers included C-reactive protein (CRP) and a panel of 20 adipokines.

Results: COPD patients had comparable fat mass but higher CRP and HOMA-IR than did control subjects. COPD patients and control subjects had comparable adipose tissue gene expression, adipocyte size, ATM infiltration, and systemic adipokine concentrations. Desaturating COPD patients had no different ATI status than did nondesaturating COPD patients. COPD patients with high CRP had significantly greater ATM infiltration than did patients with low CRP, which was independent of BMI and fat mass.

Conclusions: In COPD patients, mild-to-moderate COPD, per se, does not enhance ATI or its contribution to systemic inflammation compared with in well-matched healthy control subjects. However, to our knowledge, our study provides a first indication for a possible role of ATMs in the systemic inflammatory response in COPD that requires additional investigation. This trial was registered at www.trialregister.nl as NTR1402.

Abbreviations:

ATI
adipose tissue inflammation
ATM
adipose tissue macrophage
cDNA
complementary DNA
CLS
crown-like structure
COPD
chronic obstructive pulmonary disease
COPDD
desaturating chronic obstructive pulmonary disease
COPDND
nondesaturating chronic obstructive pulmonary disease
CRP
C-reactive protein
FFM
fat-free mass
FFMI
fat-free mass index
FM
fat mass
FMI
fat mass index
FVC
forced vital capacity
GOLD
global initiative for obstructive lung disease
IR
insulin resistance
mRNA
messenger RNA
SAT
subcutaneous adipose tissue
VAT
visceral adipose tissue

Cited by (0)

1

From the NUTRIM School for Nutrition, Toxicology and Metabolism, Department of Respiratory Medicine, Maastricht University Medical Center+, Maastricht, Netherlands (BvdB, HRG, GW, VACVH, FJS, and AMWJS), and the Center for Cellular and Molecular Intervention, Department of Pediatric Immunology, University Medical Center Utrecht, Utrecht, Netherlands (WdJ).

2

This study was performed within the framework of the Dutch Top Institute Pharma project T1-201.

3

Address reprint requests and correspondence to Bvd Borst, Department of Respiratory Medicine, Maastricht University Medical Center+, PO Box 616, 6200 MD Maastricht, Netherlands. E-mail: [email protected].