Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany.
Biomedical Research in Endstage and Obstructive Lung Disease-Hannover, German Center for Lung Research, Hannover, Germany.
Am J Respir Cell Mol Biol. 2021 Mar;64(3):379-390. doi: 10.1165/rcmb.2020-0335OC.
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.
肥胖症和 2 型糖尿病是与肺功能损害和肺部疾病相关的营养相关病症；然而，潜在的发病机制尚不完全清楚。肺表面活性剂对于肺功能至关重要，而 AT2（肺泡上皮 2 型）细胞合成肺表面活性剂依赖于营养物质的摄取。我们假设碳水化合物或脂肪的饮食含量会影响肺表面活性剂的动态平衡和组成。用富含淀粉的饮食（StD）、富含蔗糖的饮食（SuD）或富含脂肪的饮食（FaD）喂养小鼠 30 周，与富含纤维的对照饮食相比，会导致高胆固醇血症和高胰岛素血症。在 SuD 和 FaD 组中，肺力学测量显示吸气时出现粘弹性变化，表明肺表面活性剂发生改变，并且 FaD 下分离的肺表面活性剂在气液界面的界面吸附减少。特征磷脂种类的组成发生改变，包括二棕榈酰磷脂酰胆碱（PC16:0/16:0）向棕榈酰-油酰磷脂酰胆碱（PC16:0/16:1）的转移，以及在碳水化合物过量摄入时，富含肉豆蔻酸的磷脂种类（PC14:0/14:0；PC16:0/14:0）减少，以及 StD、SuD 和 FaD 组中棕榈酰-油酰-磷脂酰甘油（PG16:0/18:1）和棕榈酰-亚油酰-磷脂酰甘油（PG16:0/18:2）的比例增加，而对照饮食中则没有。此外，AT2 细胞中与肺表面活性剂合成相关的蛋白质的 mRNA 表达水平也发生了改变。在 StD 方案下，AT2 细胞表现出明显的脂质积累和较小的板层小体。因此，在已建立的小鼠模型中，不同的饮食相关肺表面活性剂改变虽然细微，但却可以检测到，并且在呼吸能力降低的情况下可能会变得具有挑战性。膳食脂肪是唯一显著影响肺表面活性剂功能的宏量营养素。这需要未来的研究来检查饮食对肺表面活性剂的影响，特别关注肥胖症和 2 型糖尿病的肺部并发症。
