The bronchoalveolar proteome changes in obesity.

Abstract

Obesity contributes to pulmonary dysfunction through poorly understood biochemical mechanisms. Chronic inflammation and altered cellular metabolism have emerged as pathological changes across organ systems in obesity, but whether similar changes occur in lungs with obesity is unknown. We collected bronchoalveolar lavage fluid (BALF) from right upper lobe and lingula pulmonary subsegments of 14 adults (7 males/7 females) with body mass indexes (BMIs) ranging from 24.3 to 50.9 kg/m² without lung disease. Proteomes were measured using sequential window acquisition of all theoretical fragment ion spectra (SWATH) mass spectrometry. Proteomic composition and pathway enrichments were examined for the cohort and as a function of BMI. BALF proteomic compositions were consistent with earlier studies and had improved protein identification. We found minimal differences in BALF proteomes between lavage regions. Five proteins were strongly correlated with BMI (False Detection Rate/FDR-adjusted P values < 0.05) and 11 had weaker correlation (FDR-adjusted P values 0.05-0.1). These proteins included acute phase reactants and complement factors. Few proteomic differences between biological sexes were detected, but some of them coincided with BMI-related proteins. Pathway enrichments impacted by BMI included innate immunity, antifibrinolysis, oxidative stress, and lipid metabolism. The bronchoalveolar microenvironment is altered by obesity in humans without lung disease. Pathway alterations associated with BMI included coagulation and fibrinolysis, redox and oxidative stress, energy metabolism, and humoral immune function. Our data support the theory that conserved biochemical and cellular changes in obesity may be fundamental mechanisms of dysfunction in multiple tissues but the specific impact on pulmonary function or disease is not yet known.NEW & NOTEWORTHY Obesity is thought to cause deleterious changes in lung biochemistry, but data in humans are lacking. We measured the alveolar proteome in bronchoalveolar lavages from subjects with a wide range of body mass index and no lung disease. We found changes in proteins and pathways associated with increasing body mass index that are similar to pathological changes observed in other tissues and may constitute mechanisms of pulmonary dysfunction in obesity.