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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

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Autor(es):
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dos Reis Rodrigues Okada, Livia Samara [1] ; Oliveira, Claudia P. [1] ; Stefano, Jose Tadeu [1] ; Nogueira, Monize Aydar [1] ; Cotrim Guerreiro da Silva, Ismael Dale [2] ; Cordeiro, Fernanda Bertucce [3] ; Ferreira Alves, Venancio Avancini [4] ; Torrinhas, Raquel Susana [1] ; Carrilho, Flair Jose [1] ; Puri, Puneet [5] ; Waitzberg, Dan L. [1]
Número total de Autores: 11
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Sch Med, Dept Gastroenterol LIM 07 LIM 35, Sao Paulo - Brazil
[2] Sao Paulo Fed Univ, Dept Gynecol, Lab Mol Gynecol, Sao Paulo, SP - Brazil
[3] Sao Paulo Fed Univ, Dept Surg, Div Urol, Human Reprod Sect, Sao Paulo - Brazil
[4] Univ Sao Paulo, Sch Med, Dept Pathol LIM 14, Sao Paulo - Brazil
[5] Virginia Commonwealth Univ, Richmond, VA - USA
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: Clinical Nutrition; v. 37, n. 5, p. 1474-1484, OCT 2018.
Citações Web of Science: 9
Resumo

Background \& 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. (C) 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved. (AU)

Processo FAPESP: 13/03742-8 - Avaliação lipidômica e proteômica de pacientes com esteato-hepatite não alcoólica (EHNA) suplementados com ácidos graxos ômega-3: estudo randomizado, duplo-cego, placebo-controlado
Beneficiário:Lívia Samara dos Reis Rodrigues
Linha de fomento: Bolsas no Brasil - Doutorado Direto
Processo FAPESP: 11/09234-9 - Avaliação lipidômica e proteômica de pacientes com esteato-hepatite não alcoólica (EHNA) suplementados com ácidos graxos ômega-3: estudo randomizado, duplo-cego, placebo-controlado
Beneficiário:Dan Linetzky Waitzberg
Linha de fomento: Auxílio à Pesquisa - Regular