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. 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.