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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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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]
Total Authors: 11
Affiliation:
[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
Total Affiliations: 5
Document type: Journal article
Source: Clinical Nutrition; v. 37, n. 5, p. 1474-1484, OCT 2018.
Web of Science Citations: 9
Abstract

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)

FAPESP's process: 13/03742-8 - Lipidomic and proteomic assessment of patients with non-alcoholic steatohepatitis (NASH) supplemented with omega-3 fatty acids: a randomized double-blind, placebo-controlled study
Grantee:Lívia Samara dos Reis Rodrigues
Support type: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 11/09234-9 - Lipidomic and proteomic assessment of patients with non-alcoholic steatohepatitis (NASH) supplemented with omega-3 fatty acids: a randomized double-blind, placebo-controlled study
Grantee:Dan Linetzky Waitzberg
Support type: Regular Research Grants