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DC Field | Value | Language |
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dc.contributor.author | López Vicario, Cristina | - |
dc.contributor.author | Alcaraz-Quiles, José | - |
dc.contributor.author | García-Alonso, Verónica | - |
dc.contributor.author | Rius, Bibiana | - |
dc.contributor.author | Hwang, Sung H. | - |
dc.contributor.author | Titos Rodríguez, Esther | - |
dc.contributor.author | Lopategi, Aritz | - |
dc.contributor.author | Hammock, Bruce D. | - |
dc.contributor.author | Arroyo, Vicente | - |
dc.contributor.author | Clària i Enrich, Joan | - |
dc.date.accessioned | 2018-04-03T15:07:58Z | - |
dc.date.available | 2018-04-03T15:07:58Z | - |
dc.date.issued | 2015-01-13 | - |
dc.identifier.issn | 0027-8424 | - |
dc.identifier.uri | http://hdl.handle.net/2445/121234 | - |
dc.description.abstract | Soluble epoxide hydrolase (sEH) is an emerging therapeutic target in a number of diseases that have inflammation as a common underlying cause. sEH limits tissue levels of cytochrome P450 (CYP) epoxides derived from omega-6 and omega-3 polyunsaturated fatty acids (PUFA) by converting these antiinflammatory mediators into their less active diols. Here, we explored the metabolic effects of a sEH inhibitor (t-TUCB) in fat-1 mice with transgenic expression of an omega-3 desaturase capable of enriching tissues with endogenous omega-3 PUFA. These mice exhibited increased CYP1A1, CYP2E1, and CYP2U1 expression and abundant levels of the omega-3-derived epoxides 17,18-epoxyeicosatetraenoic acid (17,18-EEQ) and 19,20-epoxydocosapentaenoic (19,20-EDP) in insulin-sensitive tissues, especially liver, as determined by LC-ESI-MS/MS. In obese fat-1 mice, t-TUCB raised hepatic 17,18-EEQ and 19,20-EDP levels and reinforced the omega-3-dependent reduction observed in tissue inflammation and lipid peroxidation. t-TUCB also produced a more intense antisteatotic action in obese fat-1 mice, as revealed by magnetic resonance spectroscopy. Notably, t-TUCB skewed macrophage polarization toward an antiinflammatory M2 phenotype and expanded the interscapular brown adipose tissue volume. Moreover, t-TUCB restored hepatic levels of Atg12-Atg5 and LC3-II conjugates and reduced p62 expression, indicating up-regulation of hepatic autophagy. t-TUCB consistently reduced endoplasmic reticulum stress demonstrated by the attenuation of IRE-1α and eIF2α phosphorylation. These actions were recapitulated in vitro in palmitate-primed hepatocytes and adipocytes incubated with 19,20-EDP or 17,18-EEQ. Relatively similar but less pronounced actions were observed with the omega-6 epoxide, 14,15-EET, and nonoxidized DHA. Together, these findings identify omega-3 epoxides as important regulators of inflammation and autophagy in insulin-sensitive tissues and postulate sEH as a druggable target in metabolic diseases. | - |
dc.format.extent | 6 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | National Academy of Sciences | - |
dc.relation.isformatof | Versió postprint del document publicat a: https://doi.org/10.1073/pnas.1422590112 | - |
dc.relation.ispartof | Proceedings of the National Academy of Sciences of the United States of America - PNAS, 2014, vol. 112, num. 2, p. 536-541 | - |
dc.relation.uri | https://doi.org/10.1073/pnas.1422590112 | - |
dc.rights | (c) López-Vicario, Cristina et al., 2014 | - |
dc.source | Articles publicats en revistes (Biomedicina) | - |
dc.subject.classification | Àcids grassos insaturats | - |
dc.subject.classification | Àcids grassos omega-3 | - |
dc.subject.classification | Inflamació | - |
dc.subject.classification | Teixit adipós | - |
dc.subject.classification | Malalties del fetge | - |
dc.subject.classification | Autofàgia | - |
dc.subject.classification | Obesitat | - |
dc.subject.other | Unsaturated fatty acids | - |
dc.subject.other | Omega-3 fatty acids | - |
dc.subject.other | Inflammation | - |
dc.subject.other | Adipose tissues | - |
dc.subject.other | Liver diseases | - |
dc.subject.other | Autophagy | - |
dc.subject.other | Obesity | - |
dc.title | Inhibition of soluble epoxide hydrolase modulates inflammation and autophagy in obese adipose tissue and liver. Role for omega-3 epoxides | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/acceptedVersion | - |
dc.identifier.idgrec | 645818 | - |
dc.date.updated | 2018-04-03T15:07:58Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 25550510 | - |
Appears in Collections: | Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Biomedicina) |
Files in This Item:
File | Description | Size | Format | |
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645818.pdf | 1.61 MB | Adobe PDF | View/Open |
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