Obesity and
type 2 diabetes 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 AT2 (alveolar epithelial type 2) 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 with a fiber-rich control diet. In SuD and
FaD groups, lung mechanic measurements revealed viscoelastic changes during inspiration, indicating
surfactant alterations, and interfacial adsorption of isolated
surfactant at the air-liquid interface was decreased under
FaD. The 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) on 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 than in the control diet. 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
type 2 diabetes.