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cohort·pulmonology, endocrinology, epidemiology, preclinical research, biomedical research·PMC10597776

Adipocyte dysfunction promotes lung inflammation and aberrant repair: a potential target of COPD

Frontiers in Endocrinology · 7 authors, 5 centres

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TL;DR

A human COPD cohort analysis, bioinformatics of obesity and COPD datasets, and an adipocyte-specific BMPR2 knockout mouse model were combined to explore links between obesity and COPD. The study found that BMI ≥24 was associated with decreased re-exacerbation at 3 months and 1 year in COPD patients, and that adipocyte-specific BMPR2 deficiency caused spontaneous lung injury, emphysema, and vascular remodeling in mice.

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The study combined a human COPD cohort analysis stratified by BMI, bioinformatics analyses of GEO datasets for obesity and COPD, and an adipocyte-specific BMPR2 conditional knockout (CKO) mouse model. In the clinical cohort, patients with BMI ≥24 showed decreased re-exacerbation rates at 3 months and 1 year, with lung function of the overweight group statistically superior to other groups. Bioinformatics identified inflammatory hub genes (CXCL8, MMP9, CCR5) and adipocytokine hub genes, with cytokine-associated pathways enriched in white adipose tissue of obese individuals and repair-associated pathways enhanced in COPD small airways. CKO mice spontaneously developed lung injury, emphysema, and pulmonary vascular remodeling with increased macrophage infiltration, and had dysregulated adipocytokine expression including decreased apelin and increased adipsin. The study is limited by a relatively small single-center clinical cohort, inability to measure pulmonary function in CKO mice due to premature death after weaning, and the preclinical findings awaiting further mechanistic validation.

STUDY TYPE

cohort

SPECIALTY

pulmonology

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AI pipeline

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ORIGINAL PAPER

PMC10597776

Adipocyte dysfunction promotes lung inflammation and aberrant repair: a potential target of COPD

Frontiers in Endocrinology

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ABSTRACT

Abstract Background Obesity and chronic obstructive pulmonary disease (COPD) are prevailing worldwide, bringing a heavy medical burden. Clinical and pathophysiological relationship between obesity and COPD is paradoxical and elusive. We aim to explore their inherent associations from clinical, genetic, and animal levels. Methods We performed literature review and cohort analysis of patients with COPD to compare lung function, symptom, and prognosis among different weight groups. After retrieving datasets of obesity and COPD in Gene Expression Omnibus (GEO) database, we carried out differentially expressed gene analysis, functional enrichment, protein–protein interactions network, and weighted gene co-expression network analysis. Then, we acquired paraffin-embedded lung tissues of fatty acid–binding protein 4–Cre-BMPR2 fl/fl conditional knockout (CKO) mice that were characterized by adipocyte-specific knockout of bone morphogenetic protein receptor 2 (BMPR2) for staining and analysis. Results Our cohort study reports the effect of obesity on COPD is inconsistent with previous clinical studies. Lung function of overweight group was statistically superior to that of other groups. We also found that the inflammatory factors were significantly increased hub genes, and cytokine-associated pathways were enriched in white adipose tissue of patients with obesity. Similarly, injury repair–associated genes and pathways were further enhanced in the small airways of patients with COPD. CKO mice spontaneously developed lung injury, emphysema, and pulmonary vascular remodeling, along with increased infiltration of macrophages. BMPR2-defiecient adipocytes had dysregulated expression of adipocytokines. Conclusion Inflammation and abnormal repair might be potential mechanisms of the pathological association between obesity and COPD. BMPR2-associated adipocyte dysfunction promoted lung inflammation and aberrant repair, in which adipocytokines might play a role and thus could be a promising therapeutic target. Keywords: adipocyte dysfunction, Chronic Obstructive Pulmonary Disease, lung inflammation, aberrant repair, adipocytokines

CITATION EXPORT

Si-jin Zhang, Xian-zheng Qin, Jie Zhou et al.. Adipocyte dysfunction promotes lung inflammation and aberrant repair: a potential target of COPD. Frontiers in Endocrinology. (2023). https://doi.org/10.3389/fendo.2023.1204744

AUTHORS

7 · 5 CENTRES

Si-jin Zhang, Xian-zheng Qin, Jie Zhou, Bin-feng He, Surendra Shrestha, Jing Zhang, Wei-ping Hu

1 Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
2 Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
3 Department of Hematology, Tongji Hospital of Tongji University, Tongji University School of Medicine, Tongji University, Shanghai, China
4 Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
5 Emergency Department, Om Aasha Hospital Pvt. Ltd., Dhanghadi, Nepal