Plasma Oxylipins Levels in Nonalcoholic Fatty Liver Disease.

摘要: Activation of innate immunity by gut-derived immunogens such as lipopolysaccharides (LPS) may play an important role in the pathogenesis nonalcoholic fatty liver disease (NAFLD). Whether NAFLD-associated lipid disturbances and polyunsaturated acid (PUFA) metabolism particular contribute to heightened immunity, remains be determined. To determine if oxylipins, metabolic products PUFA metabolism, enhance immune reactivity alone and/or following exposure LPS. Plasma peripheral blood mononuclear cells (PBMC) were collected from 35 NAFLD patients 8 healthy controls. Oxylipin levels documented HPLC–MS/MS, cytokines (IL-1, IL-6, IL-10, TNF-α) ELISA, chemokine receptors (CCR1 CCR2) flow cytometry. Mean plasma four pro-inflammatory oxylipins (Tetranor 12-HETE, 20-HETE, 8-HETrE, 7-HDoHE) significantly elevated compared However, did not correlate with severity injury reflected serum aminotransferases, ck18M30, Fib-4 determinations. In vitro, 20-HETE (0.01–100 nM), oxylipin most levels, alter or control PBMC cytokine release increases 24 h LPS exposure. Similarly, CCR1 CCR2 expression LPS-induced downregulation these receptors. Pro-inflammatory are increased NAFLD, but metabolites do appear drive short-term direct chemotaxis.