Dietary long-chain omega 3 fatty acids modify sphingolipid metabolism to facilitate asthmatic airway hyperreactivity

We report the effects of dietary n-3 polyunsaturated fatty acids (PUFAs) on sphingolipid metabolism and airway reactivity in the lung. Mice were fed a n3-PUFA enriched fishoil diet or an isocaloric control coconut oil-enriched diet (CO) for 8 weeks. The n-3 PUFA diet affected pulmonary sphingolipid metabolism, and airway reactivity, independent of inflammation or allergic sensitization. These findings support a role for pulmonary sphingolipid homeostasis in asthma and could have implications for the use of n-3 PUFA dietary supplements in asthma. Overall design: Female C57Bl/6 mice were fed a high-fat, semipurified diet (total 19% fat, 0.2% cholesterol, w/w) enriched in either n-3 PUFAs (91% menhaden fish oil and 9% corn oil; Harlan Teklad; TD. 07500; "FO") or saturated fat (SAT; 78% saturated fat from coconut oil, 13% monounsaturated fat from olive oil, and 9% polyunsaturated fat from corn oil; Harlan Teklad; TD. 08081; "CO") for 8 weeks. Weights and food consumption were checked weekly. After 8 weeks the animals underwent pulmonary function testing (airway reactivity), the lungs were perfused with PBS and RNA was extracted and RNA sequencing performed.

本研究报告了膳食来源n-3多不饱和脂肪酸（n-3 polyunsaturated fatty acids, PUFAs）对肺部神经鞘脂代谢（sphingolipid metabolism）与气道反应性（airway reactivity）的影响。实验小鼠分为两组，分别饲喂富含n-3多不饱和脂肪酸的鱼油膳食，或等热量对照椰子油膳食（CO），干预周期为8周。研究发现，n-3多不饱和脂肪酸膳食可影响肺部神经鞘脂代谢与气道反应性，且该效应不受炎症或过敏致敏状态的干扰。本研究结果证实了肺部神经鞘脂稳态（sphingolipid homeostasis）在哮喘发病机制中的作用，同时为n-3多不饱和脂肪酸膳食补充剂在哮喘诊疗中的应用提供了潜在参考价值。
整体实验设计：选取雌性C57BL/6小鼠，饲喂高脂半纯化膳食（总脂肪占比19%，胆固醇占比0.2%，质量比），分别添加n-3多不饱和脂肪酸来源（91%鳀鱼油+9%玉米油；Harlan Teklad公司；货号TD. 07500，下称"FO组"）或饱和脂肪来源（78%椰子油来源饱和脂肪、13%橄榄油来源单不饱和脂肪、9%玉米油来源多不饱和脂肪；Harlan Teklad公司；货号TD. 08081，下称"CO组"），干预周期为8周。每周称量小鼠体重并记录食物消耗量。干预8周后，对小鼠进行肺功能检测（气道反应性测定），随后经磷酸盐缓冲液（Phosphate Buffered Saline, PBS）灌洗肺部，提取总RNA并开展RNA测序（RNA sequencing）。