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Dietary Docosahexaenoic Acid and trans-10, cis-12-Conjugated Linoleic Acid Differentially Alter Oxylipin Profiles in Mouse Periuterine Adipose Tissue

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Lipids

Abstract

Diets containing high n-3 polyunsaturated fatty acids (PUFA) decrease inflammation and the incidence of chronic diseases including cardiovascular disease and nonalcoholic fatty liver disease while trans-fatty acids (TFA) intake increases the incidence of these conditions. Some health benefits of n-3 PUFA are mediated through the impact of their oxygenated metabolites, i.e. oxylipins. The TFA, trans-10, cis-12-conjugated linoleic acid (CLA; 18:2n-6) is associated with adipose tissue (AT) inflammation, oxidative stress, and wasting. We examined the impact of a 4-week feeding of 0, 0.5, and 1.5% docosahexaenoic acid (DHA; 22:6n-3) in the presence and absence of 0.5% CLA on AT oxylipin profiles in female C57BL/6N mice. Esterified oxylipins in AT derived from linoleic acid (LNA), alpha-linolenic acid (ALA), arachidonic acid (ARA), eicosapentaenoic acid (EPA), DHA, and putative from CLA were quantified. CLA containing diets reduced AT mass by ~62%. Compared with the control diet, the DHA diet elevated concentrations of EPA-and DHA-derived alcohols and epoxides and LNA-derived alcohols, reduced ARA-derived alcohols, ketones, epoxides, and 6-keto-prostaglandin (PG) F (P < 0.05), and had mixed effects on ALA-derived alcohols. Dietary CLA lowered EPA-, DHA-, and ALA-derived epoxides, ARA-derived ketones and epoxides, and ALA-derived alcohols. While dietary CLA induced variable effects in EPA-, DHA-, and LNA-derived alcohols and LNA-derived ketones, it elevated ARA-derived alcohols and PGF, PGF, and F2-isoprostanes. DHA counteracted CLA-induced effects in 67, 57, 43, and 29% of total DHA-, ARA-, EPA-, and ALA-derived oxylipins, respectively. Thus, CLA elevated proinflammatory oxylipins while DHA increased anti-inflammatory oxylipins and diminished concentration of CLA-induced pro-inflammatory oxylipins in AT.

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Abbreviations

ALA:

Alpha-linolenic acid (18:3n-3)

ARA:

Arachidonic acid (20:4n-6)

AT:

Adipose tissue

CLA:

trans-10, cis-12-conjugated linoleic acid (18:2n-6)

CON:

Control diet

COX:

Cyclooxygenase

CYP:

Cytochrome P450

DH:

Dehydrogenase

DHA:

Docosahexaenoic acid (22:6n-3)

DiHDoPE:

Dihydroxy-docosapentaenoic

DiHETE:

Dihydroxy-eicosatetraenoic acid

DiHETrE:

Dihydroxy-eicosatrienoic acid

DiHODE:

Dihydroxy-octadecadienoic acid

DiHOME:

Dihydroxy-octadecenoic acid

EKODE:

Epoxy-keto-octadecenoic acid

EPA:

Eicosapentaenoic acid (20:5n-3)

EpDoPE:

Epoxy-docosapentaenoic acid

EpETE:

Epoxy-eicosatetraenoic acid

EpETrE:

Epoxy-eicosatrienoic acid

EpODE:

Epoxy-octadecadienoic acid

EpOME:

Epoxy-octadecenoic acid

F2-IsoP:

F2-isoprostanes

HDoHE:

Hydroxy-docosahexaenoic acid

HEPE:

Hydroxy-eicosapentaenoic acid

HETE:

Hydroxy-eicosatetraenoic acid

HETrE:

Hydroxy-eicosatrienoic acid

HODE:

Hydroxy-octadecadienoic acid

HOTrE:

Hydroxy-octadecatrienoic acid

IL-6:

Interleukin-6

IR:

Insulin resistance

KETE:

Keto-eicosatetraenoic acid

KODE:

Keto-octadecadienoic acid

LNA:

Linoleic acid (18:2n-6)

LOX:

Lipoxygenase

NAFLD:

Nonalcoholic fatty liver disease

PG:

Prostaglandin

PUFA:

Polyunsaturated fatty acid

ROS:

Reactive oxygen species

sEH:

Soluble epoxide hydrolase

TFA:

Trans fatty acid

TNFα:

Tumor necrosis factor alpha

TriHOME:

Trihydroxy-octadecenoic acid

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Acknowledgements

The authors would like to thank Jan Peerson at the University of California Davis for statistical support. This research was supported by USDA/ARS Intramural Projects 5306-51530-017-00D, 5306-51530-019-00D and 2032-51530-022-00D.

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Correspondence to Darshan S. Kelley.

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Adkins, Y., Belda, B.J., Pedersen, T.L. et al. Dietary Docosahexaenoic Acid and trans-10, cis-12-Conjugated Linoleic Acid Differentially Alter Oxylipin Profiles in Mouse Periuterine Adipose Tissue. Lipids 52, 399–413 (2017). https://doi.org/10.1007/s11745-017-4252-3

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