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

TitleDietary long-chain omega 3 fatty acids modify sphingolipid metabolism to facilitate airway hyperreactivity.
Publication TypeJournal Article
Year of Publication2022
AuthorsHeras A, Gomi R, Young M, Chang CL, Wasserman E, Sharma A, Wu W, Gu J, Balaji U, White R, Permaul P, Janahi I, Worgall TS, Worgall S
JournalSci Rep
Date Published2022 Nov 17
KeywordsAnimals, Asthma, Diet, Fatty Acids, Fatty Acids, Omega-3, Fatty Acids, Unsaturated, Female, Inflammation, Mice, Pregnancy, Sphingolipids

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are essential nutrients that can affect 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 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.

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Alternate JournalSci Rep
PubMed ID36396956
PubMed Central IDPMC9672127
Grant ListR01 DK119389 / DK / NIDDK NIH HHS / United States
KL2 TR002385 / TR / NCATS NIH HHS / United States

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