Magnitude of obesity alone does not alter the alveolar lipidome

Abstract

Obesity may lead to pulmonary dysfunction through complex and incompletely understood cellular and biochemical effects. Altered lung lipid metabolism has been identified as a potential mechanism of lung dysfunction in obesity. Although murine models of obesity demonstrate changes in pulmonary surfactant phospholipid composition and function, data in humans are lacking. We measured untargeted shotgun lipidomes in two bronchoalveolar lavages (BALs) from apical and anteromedial pulmonary subsegments of 14 adult subjects (7 males and 7 females) with body mass indexes (BMIs) ranging from 24.3 to 50.9 kg/m². The lipidome composition was characterized at the class, species, and fatty acyl/alkyl level using total lipid molecular ion signal intensities normalized to BAL protein concentration and epithelial lining fluid volumes. Multivariate analyses were conducted to identify potential changes with increasing BMI. The alveolar lipidomes contained the expected composition of surfactant-associated phospholipids, sphingolipids, and sterols in addition to cardiolipin and intracellular signaling lipid species. No significant differences in lipidomes were detected between the two BAL regions. Though a small number of lipid species were associated with BMI in multivariate analyses, no robust differences in lipidome composition or specific lipid species were identified over the range of body habitus. The magnitude of obesity alone does not substantially alter the alveolar lipidome in patients without lung disease. Differences in lung function in patients with obesity and no lung disease are unlikely related to changes in alveolar lipid composition.NEW & NOTEWORTHY Altered lung lipid metabolism has been identified as a potential mechanism of lung dysfunction in obesity, but data in humans are lacking. We measured the alveolar lipidome in bronchoalveolar lavages from subjects with healthy lungs with a wide range of body mass index. There were no differences in lipidome composition in association with the magnitude of obesity. In patients with healthy lungs, obesity alone does not alter the alveolar lipidome.

Keywords: bronchoalveolar lavage; lipidome; lung; obesity; surfactant.

Graphical abstract

Figure 1.

Study schematic. Bronchoalveolar lavages (BAL) were obtained from right upper lobe and superior lingula pulmonary subsegments. The BAL fluid (BALF) was processed to remove cells and debris. Lipids were extracted, applied to untargeted multiple precursor ion scanning (MPIS) mass spectrometry, and lipids were identified from the ion fragments. Ion intensity data were normalized to BAL protein and epithelial lining fluid volumes and used to characterize the lipidome composition. Multivariate informatics methods were used to investigate the differences in the lipidomes between BAL regions, sex, statin use, and for changes associated with body mass index (BMI).

Figure 2.

Alveolar lipid class intensity normalized by protein. A: the protein-normalized signal intensity for surfactant-associated glycerophospholipids phosphatidylcholine (PC), phosphatidylglycerol (PG), phosphatidylethanolamine (PE), phosphatidic acid (PA), phosphatidylinositol (PI), and phosphatidylserine (PS) arranged by subject body mass index (BMI). B: protein-normalized signal intensity for sphingomyelin (SM), cardiolipins (CL), and ganglioside lipids arranged by subject BMI. C: protein-normalized signal intensity for sterols, ceramides, PI-phosphates (PIPs), triacylglycerols (TAGs), diacylglycerols (DAG), and cytidine diphosphate DAG (CDP-DAG). Each bar represents the average of the 2 BAL, except for (#), which had only one sample. Note the differences in scale for each panel. Presented as intensity count × 10⁵/natural logarithm [protein].

Figure 3.

Alveolar phospholipid fatty acid composition. A: overall distribution (top) of phosphatidylcholine (PC) fatty acid composition and individual distributions (bottom) arranged by subject body mass index (BMI). B: global distribution (top) of phosphatidylglycerol (PG) fatty acid composition and individual distributions (bottom). C: overall distribution (top) of phosphatidylethanolamine (PE) fatty acid composition and individual distributions (bottom). Colors in all panels correspond to total fatty acid chain lengths. Individual distributions are the average of the 2 bronchoalveolar lavages (BALs), except for (#), which had only one sample.

Figure 4.

Alveolar lipid fatty acid composition. A: overall distribution (top) of sphingomyelin (SM) fatty acid composition and individual distributions (bottom) arranged by subject body mass index (BMI). B: global distribution (top) of ceramide fatty acid composition and individual distributions (bottom). C: overall distribution (top) of cardiolipin (CL) fatty acid composition and individual distributions (bottom). Colors in all panels correspond to total fatty acid chain lengths. Individual distributions are the average of the 2 bronchoalveolar lavages (BALs), except for (#), which had only one sample.