Diet-induced obesity alleviates epithelial damage in hyperoxic acute lung injury (HALI) in mice

Figures

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  Fig. 1. Study design. Control diet, 11 kcal% fat; high fat diet, 60 kcal% fat; hyperoxia, FiO2 = 0.9

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  Fig. 2. Effects of diet and hyperoxia on arterial blood gases and pH. A pH; B bicarbonate; C total carbon dioxide; D carbon dioxide partial pressure; E oxygen partial pressure; F oxygen saturation. Data are presented as individual values with indicated group means and standard deviations. CD n = 7, HFD n = 7, CD-Hyper n = 7, HFD-Hyper n = 9. Statistics: 2 W-ANOVA, significant p-values or p-values showing a tendency to significance are shown above dot plots. In case of positive interaction effects, pairwise comparisons by post-hoc Tukey Test were performed; p-values < 0.05 are indicated

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  Fig. 3. Effects of diet and hyperoxia on the lung proteome. A Principal component analysis; B Venn diagram of protein changes in comparison to the CD group; C volcano plots, dashed lines represent (i) -log10 p > 1.301 and (ii) log2-fold change > 1.0 or < 1.0; proteins beyond these thresholds are color-coded in blue for reduced abundance (CD vs. HFD: 36 proteins, CD vs. CD-Hyper: 204 proteins, CD vs. HFD-Hyper: 257 proteins) and in red for increased abundance (CD vs. HFD: 30 proteins, CD vs. CD-Hyper: 287 proteins, CD vs. HFD-Hyper: 295 proteins); D pathway analysis by STRING database of differentially expressed proteins in CD-Hyper (left) or HFD-Hyper (right) compared to CD with p < 0.05 and log2-fold change > 1.0 or < 1.0, shown are Gene Ontology enrichment biological processes; E pathway analysis by STRING database of differentially expressed proteins with p < 0.05 that were uniquely altered in CD-Hyper (left) or HFD-Hyper (right) compared to CD, Gene Ontology enrichment biological processes are shown. F Volcano Plot for hyperoxic groups, dashed lines represent (i) -log10 p > 1.301 and (ii) log2-fold change > 1.0 or < 1.0; proteins beyond these thresholds are color-coded in blue for…

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  Fig. 4. Effects of diet and hyperoxia on lung mechanics and parenchymal composition. A Pressure-volume curves; B quasi-static lung compliance; C hysteresis; D left lung volume; E septal volume; F ductal airspace volume; G alveolar airspace volume. Data are presented as means (A) or individual values, with indicated group means and standard deviations (B-G). A-C CD n = 7, HFD n = 7, CD-Hyper n = 10, HFD-Hyper n = 9; D-G CD n = 7, HFD n = 7, CD-Hyper n = 10, HFD-Hyper n = 10. B-G Statistics: 2 W-ANOVA, significant p-values or p-values showing a tendency to significance are shown above dot plots. In case of positive interaction effects, pairwise comparisons by post-hoc Tukey Test were performed; p-values < 0.05 are indicated

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  Fig. 5. Effects of diet and hyperoxia on the gas exchange region. A Septal surface area; B septal thickness; C mean linear intercept length; D surface area of fragmented AE1 cells; E surface area of intact AE1 cells. F Representative image of septal ultrastructure after hyperoxia exposure, image from CD-Hyper animal; G representative image of intact septal ultrastructure, image from CD animal; endo, endothelial cell; bl, basal lamina; AE1, AE1 cell; cap, capillary; ery, erythrocyte; arrowheads in G indicate fragments of epithelial cells. H AE2 cell number; I AE1 cell volume; J AE2 cell volume. Data are presented as individual values, with indicated group means and standard deviations. CD n = 7, HFD n = 7, CD-Hyper n = 10, HFD-Hyper n = 10. Statistics: 2 W-ANOVA, significant p-values or p-values showing a tendency to significance are shown above dot plots. In case of positive interaction effects, pairwise comparisons by post-hoc Tukey Test were performed; p-values < 0.05 are indicated

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  Fig. 6. Edema formation in response to hyperoxia. A Representative light microscopic image of peribronchovascular edema (HFD-Hyper animal shown); br, bronchus; bv, blood vessel; alv, alveoli; ed, edema fluid. B, C Representative electron microscopic images of septal edema in intact septa (B; CD-Hyper animal shown) or next to fragmented AE1 cells (C; CD-Hyper animal shown); AE1, AE1 cell; endo, endothelial cell; int cell, interstitial cell; bl, basal lamina; ed, edema fluid; cap lumen, capillary lumen; +ery, with erythrocyte; arrowheads indicate fragmented AE1 cells. D Volume of septal edema; data are presented as individual values, group means and standard deviations are indicated; CD n = 7, HFD n = 7, CD-Hyper n = 10, HFD-Hyper n = 10; statistics: 2 W-ANOVA, significant p-values are shown above dot plot. E Correlation of surface area of fragmented AE1 cells with edema volume in CD-Hyper group, n = 10; linear regression indicated as line; statistics: Pearson correlation analysis, Pearsons r and p-values shown. F Volcano Plot for CD-Hyper animals with severe edema vs. other CD-Hyper animals, dashed lines represent (i) -log10 p > 1.301 and (ii) log2-fold change > 1.0 or < 1.0; proteins…