LIVIA SAMARA DOS REIS RODRIGUES OKADA

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LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina

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Autor e Coautores FMUSP-HC Normalizados: VENANCIO AVANCINI FERREIRA ALVES ×

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Agora exibindo 1 - 4 de 4
  • conferenceObject
    Plasma Proteomic Signature in Patients with Nash Treated with OMEGA-3: Perspectives of Knowing Mechanism of Action.
    (2018) OKADA, Livia Samara Reis Rodrigues; OLIVEIRA, Claudia P. M. S.; STEFANO, Jose Tadeu; NOGUEIRA, Monize Aydar; CORDEIRO, Fernanda Bertucce; ALVES, Venancio A. F.; TORRINHAS, Raquel Suzana; CARRILHO, Flair Jose; WAITZBERG, Dan Linetzky
  • article 64 Citação(ões) na Scopus
    Omega-3 PUFA modulate lipogenesis, ER stress, and mitochondrial dysfunction markers in NASH - Proteomic and lipidomic insight
    (2018) OKADA, Livia Samara dos Reis Rodrigues; OLIVEIRA, Claudia P.; STEFANO, Jose Tadeu; NOGUEIRA, Monize Aydar; SILVA, Ismael Dale Cotrim Guerreiro da; CORDEIRO, Fernanda Bertucce; ALVES, Venancio Avancini Ferreira; TORRINHAS, Raquel Susana; CARRILHO, Flair Jose; PURI, Puneet; WAITZBERG, Dan L.
    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.
  • conferenceObject
    Omega-3 fatty acids improve proteomic and lipidomic markers of endoplasmic reticulum (ER) stress and mitochondrial dysfunction in a randomized controlled trial in subjects with Nonalcoholic Steatohepatitis
    (2015) RODRIGUES, Livia; OLIVEIRA, Claudia P.; STEFANO, Jose Tadeu; NOGUEIRA, Monize A.; SILVA, Ismael D.; TURCO, Edson G. Lo; ALVES, Venancio Avancini F.; CARRILHO, Flair J.; PURI, Puneet; WAITZBERG, Dan
  • article 92 Citação(ões) na Scopus
    Omega-3 polyunsaturated fatty acids in treating non-alcoholic steatohepatitis: A randomized, double-blind, placebo-controlled trial
    (2016) NOGUEIRA, Monize Aydar; OLIVEIRA, Claudia Pinto; ALVES, Venancio Avancini Ferreira; STEFANO, Jose Tadeu; RODRIGUES, Livia Samara dos Reis; TORRINHAS, Raquel Susana; COGLIATI, Bruno; BARBEIRO, Hermes; CARRILHO, Flair Jose; WAITZBERG, Dan Linetzky
    Background: & aims: Few clinical trials have addressed the potential benefits of omega-3 polyunsaturated fatty acids (PUFAs) on non-alcoholic steatohepatitis (NASH). We evaluated the effects of supplementation with omega-3 PUFAs from flaxseed and fish oils in patients with biopsy-proven NASH. Methods: Patients received three capsules daily, each containing 0315 g of omega-3 PUFAs (64% alpha-linolenic [ALA], 16% eicosapentaenoic [EPA], and 21% docosahexaenoic [DHA] acids; n-3 group, n = 27) or mineral oil (placebo group, n = 23). Liver biopsies were evaluated histopathologically by the NASH activity score (NAS). Plasma levels of omega-3 PUFAs were assessed as a marker of intake at baseline and after 6 months of treatment. Secondary endpoints included changes in plasma biochemical markers of lipid metabolism, inflammation, and liver function at baseline and after 3 and 6 months of treatment. Results: At baseline, NAS was comparable between the groups (p = 0.98). After intervention with omega 3 PUFAs, plasma ALA and EPA levels increased (p <= 0.05). However in the placebo group, we also observed increased EPA and DHA (p <= 0.05), suggesting an off-protocol intake of PUFAs. NAS improvement/stabilization was correlated with increased ALA in the n-3 group (p = 0.02) and with increased EPA (p = 0.04) and DHA (p = 0.05) in the placebo group. Triglycerides were reduced after 3 months in the n-3 group compared to baseline (p = 0.01). Conclusions: In NASH patients, the supplementation of omega-3 PUFA from flaxseed and fish oils significantly impacts on plasma lipid profile of patients with NASH. Plasma increase of these PUFAs was associated with better liver histology.