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

Frontiers in Endocrinology

Endocrinology

Xian-zheng Qin¹  Wei-ping Hu²  Jie Zhou²  Bin-feng He²  Jing Zhang²  Si-jin Zhang³  Surendra Shrestha⁴ 

[1] Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;Department of Hematology, Tongji Hospital of Tongji University, Tongji University School of Medicine, Tongji University, Shanghai, China;Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;Emergency Department, Om Aasha Hospital Pvt. Ltd., Dhanghadi, Nepal;

关键词: adipocyte dysfunction;    Chronic Obstructive Pulmonary Disease;    lung inflammation;    aberrant repair;    adipocytokines;   

DOI  :  10.3389/fendo.2023.1204744

 received in 2023-04-12, accepted in 2023-09-18,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundObesity 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.MethodsWe 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-BMPR2fl/fl conditional knockout (CKO) mice that were characterized by adipocyte-specific knockout of bone morphogenetic protein receptor 2 (BMPR2) for staining and analysis.ResultsOur 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.ConclusionInflammation 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.

【 授权许可】

Unknown   
Copyright © 2023 Zhang, Qin, Zhou, He, Shrestha, Zhang and Hu