Omega-3 PUFA modulate lipogenesis, ER stress, and mitochondrial dysfunction markers in NASH - Proteomic and lipidomic insight

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorOKADA, Livia Samara dos Reis Rodrigues
dc.contributor.authorOLIVEIRA, Claudia P.
dc.contributor.authorSTEFANO, Jose Tadeu
dc.contributor.authorNOGUEIRA, Monize Aydar
dc.contributor.authorSILVA, Ismael Dale Cotrim Guerreiro da
dc.contributor.authorCORDEIRO, Fernanda Bertucce
dc.contributor.authorALVES, Venancio Avancini Ferreira
dc.contributor.authorTORRINHAS, Raquel Susana
dc.contributor.authorCARRILHO, Flair Jose
dc.contributor.authorPURI, Puneet
dc.contributor.authorWAITZBERG, Dan L.
dc.date.accessioned2018-11-21T17:01:29Z
dc.date.available2018-11-21T17:01:29Z
dc.date.issued2018
dc.description.abstractBackground & aims: Currently there is no FDA-approved therapy for nonalcoholic steatohepatitis (NASH). Increased n-6/n-3 polyunsaturated fatty acids (PUFA) ratio can induce endoplasmic reticulum (ER) stress and mitochondrial dysfunction that characterize NASH. Our recent study with n-3 PUFA showed improvement in individual histologic parameters like steatosis, ballooning and lobular inflammation. We hypothesized that n-3 PUFA therapy mediated improvement in histologic parameters is modulated by lipidomic and proteomic changes. Methods: We therefore evaluated hepatic proteomic and plasma lipidomic profiles before and after n-3 PUFA therapy in subjects with NASH. In a double-blind, randomized, placebo-controlled trial, patients with NASH received 6-month treatment with n-3 PUFA (0.945 g/day [64% alpha-linolenic (ALA), 21% eicosapentaenoic (EPA), and 16% docosahexaenoic (DHA) acids]). Paired liver biopsy and plasma collected before and after-n-3 PUFA therapy were assessed using mass spectrometry and gas chromatography for hepatic proteomics and plasma lipidomics. Data were matched to UniProt and LIPID MAPS database, respectively. Cytoscape software was used to analyze functional pathways. Twenty-seven NASH patients with paired liver histology and plasma before and after n-3 PUFA treatment were studied. Results: Treatment with n-3 PUFA significantly increased ALA, EPA, and glycerophospholipids, and decreased arachidonic acid (p < 0.05 for all). Further, proteomic markers of cell matrix, lipid metabolism, ER stress and cellular respiratory pathways were also modulated. Interestingly, these alterations reflected functional changes highly suggestive of decreased cellular lipotoxicity potential; reduced ER proteasome degradation of proteins and induction of chaperones; and a shift in cell energy homeostasis towards mitochondrial beta-oxidation. Conclusion: Six-month treatment with omega-3 PUFAs significantly improved hepatic proteomic and plasma lipidomic markers of lipogenesis, endoplasmic reticulum stress and mitochondrial functions in patients with NASH.
dc.description.indexMEDLINE
dc.description.sponsorshipFundacao de Amparo a Pesquisa do Estado de Sao Paulo [2011/09234-9, 2013/03742-8]
dc.identifier.citationCLINICAL NUTRITION, v.37, n.5, p.1474-1484, 2018
dc.identifier.doi10.1016/j.clnu.2017.08.031
dc.identifier.eissn1532-1983
dc.identifier.issn0261-5614
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/29464
dc.language.isoeng
dc.publisherCHURCHILL LIVINGSTONE
dc.relation.ispartofClinical Nutrition
dc.rightsrestrictedAccess
dc.rights.holderCopyright CHURCHILL LIVINGSTONE
dc.subjectOmega-3 PUFA
dc.subjectNASH
dc.subjectProteomic
dc.subjectLipidomic
dc.subjectMitochondrial dysfunction
dc.subjectEndoplasmic reticulum stress
dc.subject.othernonalcoholic fatty liver
dc.subject.otherendoplasmic-reticulum stress
dc.subject.otherbinding protein
dc.subject.otherenergy homeostasis
dc.subject.otherhepatic steatosis
dc.subject.otherdisease
dc.subject.otheracid
dc.subject.othersteatohepatitis
dc.subject.othercells
dc.subject.othergene
dc.subject.wosNutrition & Dietetics
dc.titleOmega-3 PUFA modulate lipogenesis, ER stress, and mitochondrial dysfunction markers in NASH - Proteomic and lipidomic insight
dc.typearticle
dc.type.categoryoriginal article
dc.type.versionpublishedVersion
dspace.entity.typePublication
hcfmusp.affiliation.countryEstados Unidos
hcfmusp.affiliation.countryisous
hcfmusp.author.externalNOGUEIRA, Monize Aydar:Univ Sao Paulo, Sch Med, Dept Gastroenterol LIM 07 LIM 35, Sao Paulo, Brazil
hcfmusp.author.externalSILVA, Ismael Dale Cotrim Guerreiro da:Sao Paulo Fed Univ, Dept Gynecol, Lab Mol Gynecol, Sao Paulo, SP, Brazil
hcfmusp.author.externalCORDEIRO, Fernanda Bertucce:Sao Paulo Fed Univ, Dept Surg, Div Urol, Human Reprod Sect, Sao Paulo, Brazil
hcfmusp.author.externalPURI, Puneet:Virginia Commonwealth Univ, Richmond, VA USA
hcfmusp.citation.scopus64
hcfmusp.contributor.author-fmusphcLIVIA SAMARA DOS REIS RODRIGUES OKADA
hcfmusp.contributor.author-fmusphcCLAUDIA PINTO MARQUES SOUZA DE OLIVEIRA
hcfmusp.contributor.author-fmusphcJOSE TADEU STEFANO
hcfmusp.contributor.author-fmusphcVENANCIO AVANCINI FERREIRA ALVES
hcfmusp.contributor.author-fmusphcRAQUEL SUSANA MATOS DE MIRANDA TORRINHAS
hcfmusp.contributor.author-fmusphcFLAIR JOSE CARRILHO
hcfmusp.contributor.author-fmusphcDAN LINETZKY WAITZBERG
hcfmusp.description.beginpage1474
hcfmusp.description.endpage1484
hcfmusp.description.issue5
hcfmusp.description.volume37
hcfmusp.origemWOS
hcfmusp.origem.pubmed29249532
hcfmusp.origem.scopus2-s2.0-85039435885
hcfmusp.origem.wosWOS:000447578700005
hcfmusp.publisher.cityEDINBURGH
hcfmusp.publisher.countrySCOTLAND
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