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

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

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Abstract Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are essential nutrients that can affect Potato Masher inflammatory responses.While n-3 PUFAs are generally considered beneficial for cardiovascular disease and obesity, the effects on asthma, the most common inflammatory lung disease are unclear.While prenatal dietary n-3 PUFAs decrease the risk for childhood wheezing, postnatal dietary n-3 PUFAs can worsen allergic airway inflammation.Sphingolipid metabolism is also affected by dietary n-3 PUFAs.

Decreased sphingolipid synthesis leads to airway hyperreactivity, besides inflammation, a cardinal feature of asthma, and common genetic asthma risk alleles lead to lower sphingolipid synthesis.We investigated the effect of dietary n-3 PUFAs on sphingolipid metabolism and airway reactivity.Comparing a fish-oil diet with a high n-3 PUFA content (FO) to an 6m isocaloric coconut oil-enriched diet (CO), we found an n-3 PUFA-dependent effect on increased airway reactivity, that was not accompanied by inflammation.Lung and whole blood content of dihydroceramides, ceramides, sphingomyelins, and glucosylceramides were lower in mice fed the n-3 PUFA enriched diet consistent with lower sphingolipid synthesis.

In contrast, phosphorylated long chain bases such as sphingosine 1-phosphate were increased.These findings suggest that dietary n-3 PUFAs affect pulmonary sphingolipid composition to favor innate airway hyperreactivity, independent of inflammation, and point to an important role of n-3 PUFAs in sphingolipid metabolism.