Omega-3 PUFA modulate lipogenesis, ER stress, and mitochondrial dysfunction markers in NASH - Proteomic and lipidomic insight
Okada LSDRR, Oliveira CP, Stefano JT, Nogueira MA, Silva IDCGD, Cordeiro FB, Alves VAF, Torrinhas RS, Carrilho FJ, Puri P, Waitzberg DL
Clinical nutrition (Edinburgh, Scotland) · 79 citas
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Cómo se estudió
- Diseño
- Ensayo controlado aleatorizado (indexado por PubMed)
- Estudiado en
- Personas
- Resultado principal
- Solo mecanismos
Quién lo pagó
- Financiación
- Financiación independiente
- Gobierno
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Subvenciones
- Fundação de Amparo à Pesquisa do Estado de São Paulo (2013/03742-8); Fundação de Amparo à Pesquisa do Estado de São Paulo (11/09234-9)
Según 1 financiador declarado.
Publicación
- Publicado
- 2017-09-08 · Clin Nutr · vol. 37 · número 5 · págs. 1474–1484
- Editorial
- Elsevier BV
- Citado
- 92 citas · más que el 96% de estudios similares · 5.0× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 39 trabajos
- Acceso
- De pago
- Áreas de investigación
- Fatty Acid Research and Health · Liver Disease Diagnosis and Treatment · Aquaculture Nutrition and Growth
- Palabras clave
- nonalcoholic steatohepatitis, omega-3 polyunsaturated fatty acids, lipogenesis, endoplasmic reticulum stress, mitochondrial dysfunction, plasma lipidomics, alpha-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, arachidonic acid, glycerophospholipids, lipotoxicity, molecular chaperones, mitochondrial beta-oxidation, energy homeostasis, n-6/n-3 PUFA ratio
- MeSH
- liver, mitochondria, humans, fatty acids, omega-3, double-blind method, proteomics, middle aged, female, male, lipogenesis, lipid metabolism, endoplasmic reticulum stress, non-alcoholic fatty liver disease, biomarkers
11 autores
- Livia Samara dos Reis Rodrigues Okada🇧🇷Universidade de São Paulo
- Claudia Pinto Marques Souza de Oliveira🇧🇷 · autor de correspondenciaUniversidade de São Paulo
- José Tadeu Stefano🇧🇷Universidade de São Paulo
- Monize Aydar Nogueira🇧🇷Universidade de São Paulo
- Ismael Dale Cotrim Guerreiro da Silva🇧🇷Universidade Federal de São Paulo
- Fernanda Bertuccez Cordeiro🇧🇷Universidade Federal de São Paulo
- Venâncio Avancini Ferreira Alves🇧🇷Universidade de São Paulo
- Raquel Susana Torrinhas🇧🇷Universidade de São Paulo
- Flair José Carrilho🇧🇷Universidade de São Paulo
- Puneet Puri🇺🇸Virginia Commonwealth University
- Dan Linetzky Waitzberg🇧🇷 · autor de correspondenciaUniversidade de São Paulo
Resumen
El texto original del estudio, en el idioma en que se publicó.
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.
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