Abstract | BACKGROUND AND PURPOSE: 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.
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Authors | Chunjiong Wang, Wenli Liu, Liu Yao, Xuejiao Zhang, Xu Zhang, Chenji Ye, Hongfeng Jiang, Jinlong He, Yi Zhu, Ding Ai |
Journal | British journal of pharmacology
(Br J Pharmacol)
Vol. 174
Issue 14
Pg. 2358-2372
(Jul 2017)
ISSN: 1476-5381 [Electronic] England |
PMID | 28471490
(Publication Type: Journal Article)
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Copyright | © 2017 The British Pharmacological Society. |
Chemical References |
- Arachidonic Acids
- 17,18-epoxy-5,8,11,14-eicosatetraenoic acid
- 5-hydroxy-6,8,11,14,17-eicosapentaenoic acid
- Eicosapentaenoic Acid
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Topics |
- Animals
- Arachidonic Acids
(administration & dosage, metabolism, pharmacology)
- Eicosapentaenoic Acid
(administration & dosage, analogs & derivatives, metabolism, pharmacology)
- Macrophages
(drug effects, metabolism)
- Mice
- Mice, Inbred C57BL
- Non-alcoholic Fatty Liver Disease
(metabolism, pathology, prevention & control)
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