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Hydroxyeicosapentaenoic acids and epoxyeicosatetraenoic acids attenuate early occurrence of nonalcoholic fatty liver disease.

Abstract：

BACKGROUND AND PURPOSE:The ω-3 polyunsaturated fatty acids (PUFAs) mediate protective effects on several metabolic disorders. However, the functions of their metabolites in the early stage of nonalcoholic fatty liver disease (NAFLD) are largely unknown. EXPERIMENTAL APPROACH:Mice were fed a control diet, high-fat diet (HFD) or ω-3 PUFA-enriched HFD (ω3HFD) for 4 days and phenotypes were analysed. LC-MS/MS was used to determine the eicosanoid profiles. Primary hepatocytes and peritoneal macrophages were used for the mechanism study. KEY RESULTS:In short-term HFD-fed mice, the significantly increased lipid accumulation in the liver was reversed by ω-3 PUFA supplementation. Metabolomics showed that the plasma concentrations of hydroxyeicosapentaenoic acids (HEPEs) and epoxyeicosatetraenoic acids (EEQs) were reduced by a short-term HFD and markedly increased by the ω3HFD. However, HEPE/EEQ treatment had no direct protective effect on hepatocytes. ω3HFD also significantly attenuated HFD-induced adipose tissue inflammation. Furthermore, the expression of pro-inflammatory cytokines and activation of the JNK pathway induced by palmitate were suppressed by HEPEs and EEQs in macrophages. 17,18-EEQ, 5-HEPE and 9-HEPE were identified as the effective components among these metabolites, as indicated by their greater suppression of the palmitate-induced expression of inflammatory factors, chemotaxis and JNK activation compared to other metabolites in macrophages. A mixture of 17,18-EEQ, 5-HEPE and 9-HEPE significantly ameliorated the short-term HFD-induced accumulation of macrophages in adipose tissue and hepatic steatosis. CONCLUSION AND IMPLICATIONS:17,18-EEQ, 5-HEPE and 9-HEPE may be potential approaches to prevent NAFLD in the early stage by inhibiting the inflammatory response in adipose tissue macrophages via JNK signalling.

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

Wang C,Liu W,Yao L,Zhang X,Zhang X,Ye C,Jiang H,He J,Zhu Y,Ai D

doi

10.1111/bph.13844

subject

Has Abstract

pub_date

2017-07-01 00:00:00

pages

2358-2372

issue

eissn

0007-1188

issn

1476-5381

journal_volume

174

pub_type

杂志文章

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Hydroxyeicosapentaenoic acids and epoxyeicosatetraenoic acids attenuate early occurrence of nonalcoholic fatty liver disease.