Plasma Oxylipins Levels in Nonalcoholic Fatty Liver Disease
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ORIGINAL ARTICLE
Plasma Oxylipins Levels in Nonalcoholic Fatty Liver Disease Qian Li1 · Julia D. Rempel1 · Terry B. Ball2 · Harold Aukema3 · Gerald Y. Minuk1 Received: 3 October 2019 / Accepted: 18 January 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Background Activation of innate immunity by gut-derived immunogens such as lipopolysaccharides (LPS) may play an important role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Whether NAFLD-associated lipid disturbances and polyunsaturated fatty acid (PUFA) metabolism in particular contribute to heightened innate immunity, remains to be determined. Objective To determine if oxylipins, metabolic products of PUFA metabolism, enhance innate immune reactivity alone and/ or following exposure to LPS. Methods Plasma and peripheral blood mononuclear cells (PBMC) were collected from 35 NAFLD patients and 8 healthy controls. Oxylipin levels were documented by HPLC–MS/MS, cytokines (IL-1, IL-6, IL-10, and TNF-α) by ELISA, and chemokine receptors (CCR1 and CCR2) by flow cytometry. Results Mean plasma levels of four pro-inflammatory oxylipins (Tetranor 12-HETE, 20-HETE, 8-HETrE, and 7-HDoHE) were significantly elevated in NAFLD patients compared to healthy controls. However, the levels did not correlate with the severity of liver injury as reflected by serum aminotransferases, ck18M30, and Fib-4 determinations. In vitro, 20-HETE (0.01–100 nM), the plasma oxylipin with the most significantly elevated plasma levels, did not alter NAFLD or control PBMC cytokine release or enhance the increases in cytokine release following 24 h of LPS exposure. Similarly, 20-HETE alone did not alter PBMC CCR1 or CCR2 expression or LPS-induced downregulation of these receptors. Conclusions Pro-inflammatory oxylipin levels are increased in NAFLD, but these metabolites do not appear to drive shortterm direct or LPS-induced increases in PBMC cytokine release or chemotaxis. Keywords Oxylipins · PUFA · Eicosanoids · NAFLD · Cytokines · Chemotaxis · Liver disease Abbreviations LPS Lipopolysaccharides NAFLD Nonalcoholic fatty liver disease PUFA Polyunsaturated fatty acid PBMC Peripheral blood mononuclear cells AA Arachidonic acid Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10620-020-06095-8) contains supplementary material, which is available to authorized users. * Gerald Y. Minuk [email protected] 1
Morberg Family Chair in Hepatology, Section of Hepatology, Department of Medicine, John Buhler Research Centre, University of Manitoba, 715 McDermot Ave., Winnipeg, MB R3E 3P4, Canada
2
Medical Microbiology and Immunology, University of Manitoba, Winnipeg, MB, Canada
3
Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, MB, Canada
COX Cyclooxygenases LOX Lipoxygenases CYP Cytochrome P450 CCR Chemokine receptors HC Healthy controls ELISAs Enzyme-linked immune absorbent assays FMO Fluorochrome minus one condition LA Linoleic acid γLA γ-linoleni
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