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

Autor: Okada LSDRR; Department of Gastroenterology (LIM-07/LIM-35), University of Sao Paulo School of Medicine, Sao Paulo, Brazil., Oliveira CP; Department of Gastroenterology (LIM-07/LIM-35), University of Sao Paulo School of Medicine, Sao Paulo, Brazil. Electronic address: claudia.oliveira220@fm.usp.br., Stefano JT; Department of Gastroenterology (LIM-07/LIM-35), University of Sao Paulo School of Medicine, Sao Paulo, Brazil., Nogueira MA; Department of Gastroenterology (LIM-07/LIM-35), University of Sao Paulo School of Medicine, Sao Paulo, Brazil., Silva IDCGD; Laboratory of Molecular Gynecology, Department of Gynecology, Sao Paulo Federal University, São Paulo, SP, Brazil., Cordeiro FB; Human Reproduction Section, Division of Urology, Department of Surgery, Sao Paulo Federal University, São Paulo, Brazil., Alves VAF; Department of Pathology (LIM-14), University of Sao Paulo School of Medicine, Sao Paulo, Brazil., Torrinhas RS; Department of Gastroenterology (LIM-07/LIM-35), University of Sao Paulo School of Medicine, Sao Paulo, Brazil., Carrilho FJ; Department of Gastroenterology (LIM-07/LIM-35), University of Sao Paulo School of Medicine, Sao Paulo, Brazil., Puri P; Virginia Commonwealth University-VCU, Richmond, VA, USA., Waitzberg DL; Department of Gastroenterology (LIM-07/LIM-35), University of Sao Paulo School of Medicine, Sao Paulo, Brazil. Electronic address: dan@ganep.com.br.
Jazyk: angličtina
Zdroj: Clinical nutrition (Edinburgh, Scotland) [Clin Nutr] 2018 Oct; Vol. 37 (5), pp. 1474-1484. Date of Electronic Publication: 2017 Sep 07.
DOI: 10.1016/j.clnu.2017.08.031
Abstrakt: 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.
(Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)
Databáze: MEDLINE
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