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The partitioning of newly assimilated linoleic and α‐linolenic acids between synthesis of longer-chain polyunsaturated fatty acids and hydroxyoctadecaenoic acids is a putative branch point in T cell essential fatty acid metabolism

The partitioning of newly assimilated linoleic and α‐linolenic acids between synthesis of longer-chain polyunsaturated fatty acids and hydroxyoctadecaenoic acids is a putative branch point in T cell essential fatty acid metabolism
The partitioning of newly assimilated linoleic and α‐linolenic acids between synthesis of longer-chain polyunsaturated fatty acids and hydroxyoctadecaenoic acids is a putative branch point in T cell essential fatty acid metabolism
Longer chain polyunsaturated fatty acids (LCPUFA) ≥ 20 carbons long are required for leukocyte function. These can be obtained from the diet, but there is some evidence that leukocytes can convert essential fatty acids (EFA) into LCPUFA. We used stable isotope tracers to investigate LCPUFA biosynthesis, and the effect of different EFA substrate ratios, in human T lymphocytes. CD3+ T cells were incubated for up to 48 hours with or without concanavalin A in media containing a 18:2n-6 : 18:3n-3 (EFA) ratio of either 5:1 or 8:1, and [13C]18:3n-3 plus [d5]18:2n-6. Mitogen stimulation increased the amounts of 16:1n 7, 18:1n 9, 18:2n 6, 20:3n 6, 20:4n 6, 18:3n 3 and 20:5n 3 in T cells. Expression of the activation marker CD69 preceded increased FADS2 and FADS1 mRNA expression, and increased amounts of [d5]20:2n 6 and [13C]20:3n 3 at 48 hours. 22 carbon n 6 or n 3 LCPUFA synthesis was not detected, consistent with the absence of ELOVL2 expression. An EFA ratio of 8:1 reduced 18:3n 3 conversion and enhanced 20:2n 6 synthesis compared to a 5:1 ratio. [d5]9- and [d5]-13-hydroxyoctadecadienoic (HODE) and [13C]9- and [13C]13-hydroxyoctadecatrienoic acids (HOTrE) were the major labelled oxylipins in culture supernatants; labelled oxylipins ≥ 20 carbons were not detected. An EFA ratio of 8:1 suppressed 9- and 13-HOTrE synthesis, but there was no significant effect on 9- and 13-HODE synthesis. These findings suggest that partitioning of newly assimilated EFA between LCPUFA synthesis and hydroxyoctadecaenoic acid may be a metabolic branch point in T cell EFA metabolism that has implications for understanding the effects of dietary fats on T lymphocyte function.
T lymphocyte, Omega-3, Omega-6, oxylipin, Polyunsaturated fatty acids, Desaturase, Elongase, Stable isotope, Cell proliferation, FADS2, ELOVL5
1664-3224
Von Gerichten, Johanna
91e9d046-0eda-4425-9456-3edd372146a3
West, Annette
e8dacc1a-5fdc-4a4f-92d8-608f2ea2994c
Irvine, Nicola
ed181be8-0435-49b7-bbc9-ddf2249fd2aa
Miles, Elizabeth
20332899-ecdb-4214-95bc-922dde36d416
Calder, Philip
1797e54f-378e-4dcb-80a4-3e30018f07a6
Lillycrop, Karen
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Fielding, Barbara
abfc6274-5a80-43de-a5c0-ccef25005f39
Burdge, Graham
09d60a07-8ca1-4351-9bf1-de6ffcfb2159
Von Gerichten, Johanna
91e9d046-0eda-4425-9456-3edd372146a3
West, Annette
e8dacc1a-5fdc-4a4f-92d8-608f2ea2994c
Irvine, Nicola
ed181be8-0435-49b7-bbc9-ddf2249fd2aa
Miles, Elizabeth
20332899-ecdb-4214-95bc-922dde36d416
Calder, Philip
1797e54f-378e-4dcb-80a4-3e30018f07a6
Lillycrop, Karen
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Fielding, Barbara
abfc6274-5a80-43de-a5c0-ccef25005f39
Burdge, Graham
09d60a07-8ca1-4351-9bf1-de6ffcfb2159

Von Gerichten, Johanna, West, Annette, Irvine, Nicola, Miles, Elizabeth, Calder, Philip, Lillycrop, Karen, Fielding, Barbara and Burdge, Graham (2021) The partitioning of newly assimilated linoleic and α‐linolenic acids between synthesis of longer-chain polyunsaturated fatty acids and hydroxyoctadecaenoic acids is a putative branch point in T cell essential fatty acid metabolism. Frontiers in Immunology, 12, [740749]. (doi:10.3389/fimmu.2021.740749). (In Press)

Record type: Article

Abstract

Longer chain polyunsaturated fatty acids (LCPUFA) ≥ 20 carbons long are required for leukocyte function. These can be obtained from the diet, but there is some evidence that leukocytes can convert essential fatty acids (EFA) into LCPUFA. We used stable isotope tracers to investigate LCPUFA biosynthesis, and the effect of different EFA substrate ratios, in human T lymphocytes. CD3+ T cells were incubated for up to 48 hours with or without concanavalin A in media containing a 18:2n-6 : 18:3n-3 (EFA) ratio of either 5:1 or 8:1, and [13C]18:3n-3 plus [d5]18:2n-6. Mitogen stimulation increased the amounts of 16:1n 7, 18:1n 9, 18:2n 6, 20:3n 6, 20:4n 6, 18:3n 3 and 20:5n 3 in T cells. Expression of the activation marker CD69 preceded increased FADS2 and FADS1 mRNA expression, and increased amounts of [d5]20:2n 6 and [13C]20:3n 3 at 48 hours. 22 carbon n 6 or n 3 LCPUFA synthesis was not detected, consistent with the absence of ELOVL2 expression. An EFA ratio of 8:1 reduced 18:3n 3 conversion and enhanced 20:2n 6 synthesis compared to a 5:1 ratio. [d5]9- and [d5]-13-hydroxyoctadecadienoic (HODE) and [13C]9- and [13C]13-hydroxyoctadecatrienoic acids (HOTrE) were the major labelled oxylipins in culture supernatants; labelled oxylipins ≥ 20 carbons were not detected. An EFA ratio of 8:1 suppressed 9- and 13-HOTrE synthesis, but there was no significant effect on 9- and 13-HODE synthesis. These findings suggest that partitioning of newly assimilated EFA between LCPUFA synthesis and hydroxyoctadecaenoic acid may be a metabolic branch point in T cell EFA metabolism that has implications for understanding the effects of dietary fats on T lymphocyte function.

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von Gerichten Front Immunol 2021 - Version of Record
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Accepted/In Press date: 8 September 2021
Keywords: T lymphocyte, Omega-3, Omega-6, oxylipin, Polyunsaturated fatty acids, Desaturase, Elongase, Stable isotope, Cell proliferation, FADS2, ELOVL5

Identifiers

Local EPrints ID: 451496
URI: http://eprints.soton.ac.uk/id/eprint/451496
ISSN: 1664-3224
PURE UUID: 37e2486c-20ed-421e-8e47-4730026d7f38
ORCID for Elizabeth Miles: ORCID iD orcid.org/0000-0002-8643-0655
ORCID for Philip Calder: ORCID iD orcid.org/0000-0002-6038-710X
ORCID for Karen Lillycrop: ORCID iD orcid.org/0000-0001-7350-5489
ORCID for Graham Burdge: ORCID iD orcid.org/0000-0002-7665-2967

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Date deposited: 04 Oct 2021 16:30
Last modified: 06 Oct 2021 01:35

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Contributors

Author: Johanna Von Gerichten
Author: Annette West
Author: Nicola Irvine
Author: Elizabeth Miles ORCID iD
Author: Philip Calder ORCID iD
Author: Karen Lillycrop ORCID iD
Author: Barbara Fielding
Author: Graham Burdge ORCID iD

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