Differential Effects of High-Fat or High-Sucrose Diet on Alveolar Epithelial Type II Cells in the Mouse Lung

Obesity poses an increasing global health issue and is a risk factor for respiratory diseases like asthma or COPD. The objective of this study was to determine obesity-related effects induced by high-fat diet (HFD) and high-sucrose diet (HSD) on alveolar type II (AE2) cells in the mouse lung. Male C57BL/6N mice were fed a purified control diet (CD-P), a non-purified (chow) control diet (CD-C), HFD or HSD for 30 weeks (n = 8 – 9). Left lungs were instillation-fixed and processed according to design-based stereological standards. The samples were analyzed using light and electron microscopy. Body weight was significantly elevated in the HSD and HFD groups compared to both control groups. Left lung volume and parenchyma volume were significantly higher only in HFD compared to control groups and HSD. The total AE2 cell number and the total septal surface area were significantly elevated in HFD-fed animals compared to both control groups and HSD. The number of AE2 cells per square millimeter of septal surface was significantly lower in CD-C compared to all the other groups. Within AE2 cells, the total volume of lamellar bodies was significantly lower in animals fed CD-P compared to CD-C. The volume-to-surface ratio of lamellar bodies was significantly lower in animals fed HFD and CD-P compared to CD-C, and significantly higher in HSD compared to CD-P, indicating differences in lamellar body size between the groups. The total volume of lipid droplets was significantly higher in animals fed CD-P in comparison to all other diets, and HSD-fed animals showed significantly increased lipid droplet accumulation compared to CD-C. In conclusion, CD-C led to lower body weight and lower lipid droplet accumulation compared to CD-P, indicating a healthier state of the CD-C control group. Moreover, the septal surface area supplied by one AE2 cell was larger and lamellar body volume was higher in CD-C when compared to all other groups. HFD induced the most prominent increases in weight, lung volume, septal surface area and AE2 cell number. However, only CD-P and HSD led to increased lipid accumulation in AE2 cells. Thus, AE2 cell specific lipid accumulation seems to be influenced by other factors rather than lung volume or body mass. Lamellar body volume was lowest in animals fed CD-P and highest in CD-C, as opposed to lipid droplet volume, suggesting an inverse correlation between intracellular lipid accumulation and surfactant synthesis.