Obesity and type 2 diabetes (T2D) are nutrition-related conditions associated with lung function impairment and pulmonary diseases; however, the underlying pathomechanisms are incompletely understood. Pulmonary surfactant is essential for lung function, and surfactant synthesis by alveolar epithelial type 2 (AT2) cells relies on nutrient uptake. We hypothesized that dietary amounts of carbohydrates or fat affect surfactant homeostasis and composition. Feeding mice a starch-rich diet (StD), sucrose-rich diet (SuD) or fat-rich diet (FaD) for 30 weeks resulted in hypercholesterolemia and hyperinsulinemia compared to a fiber-rich control diet (CD). In SuD and FaD groups, lung mechanics measurements revealed viscoelastic changes during inspiration indicating surfactant alterations, and interfacial adsorption of isolated surfactant at the air-liquid interface was decreased under FaD. Composition of characteristic phospholipid species was modified, including a shift from dipalmitoyl-phosphatidylcholine (PC16:0/16:0) to palmitoyl-palmitoleoyl-phosphatidylcholine (PC16:0/16:1) in response to carbohydrates and decreased myristic acid containing phosphatidylcholine species (PC14:0/14:0, PC16:0/14:0) upon excess fat intake, as well as higher palmitoyl-oleoyl-phosphatidylglycerol (PG16:0/18:1) and palmitoyl-linoleoyl-phosphatidylglycerol (PG16:0/18:2) fractions in StD, SuD and FaD groups compared to CD. Moreover, mRNA expression levels of surfactant synthesis-related proteins within AT2 cells were altered. Under the StD regimen, AT2 cells showed prominent lipid accumulations and smaller lamellar bodies. Thus, in an established mouse model distinct diet-related surfactant alterations were subtle yet detectable, and may become challenging under conditions of reduced respiratory capacity. Dietary fat was the only macronutrient significantly affecting surfactant function. This warrants future studies examining alimentary effects on lung surfactant, with special regard to pulmonary complications in obesity and T2D.
- Schipke, J.
- Jütte, D.
- Brandenberger, C.
- Autilio, C.
- Perez-Gil, J.
- Bernhard, W.
- Ochs, M.
- Mühlfeld, C.
Keywords
- Diet composition
- Lung lipid metabolism
- Obesity
- Pulmonary surfactant