Lipidomic and proteomic assessment of patients with non-alcoholic steatohepatitis (NASH) supplemented with omega-3 fatty acids: a randomized double-blind, placebo-controlled study

• Grant number: 11/09234-9
• Support Opportunities: Regular Research Grants
• Duration: November 01, 2011 - October 31, 2014
• Field of knowledge: Health Sciences - Nutrition - Nutrition Biochemistry
• Principal Investigator: Dan Linetzky Waitzberg
• Grantee: Dan Linetzky Waitzberg
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Claudia Pinto Marques Souza de Oliveira ; Elizabeth Aparecida Ferraz da Silva Torres ; Ismael Dale Cotrim Guerreiro da Silva ; Lívia Samara dos Reis Rodrigues Okada ; Raquel Susana Matos de Miranda Torrinhas ; Venancio Avancini Ferreira Alves

Abstract

The capacity to modulate inflammatory response and the metabolism of fatty acids of polyunsaturated fatty acids omega-3 (PUFA n-3) have shown benefits in controlling steatosis and the production of metabolic and inflammatory responses markers in NAFLD/NASH. The mechanisms associated with these benefits remain poorly understood. This study aims to evaluate the metabolomic profile of patients with NASH supplemented with PUFA n-3 . This assessment will be developed in liver biopsies and plasma samples collected in a preliminary double blind clinical trial at the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, which evaluated the clinical effect of supplementation with omega-3 fatty acids in the treatment of NASH. This preliminary study involved adult NASH patients of both sexes that were randomly assigned to two groups: Group1. group treatment: treated with daily supplementation with 3 capsules containing a mixture of linseed oil and fish oil (0.315 g PUFA, and 0,065 g n-3 EPA, 0,050 g n-3 DHA and 0.2 g alpha-linolenic acid per capsule), equivalent to a total of 945 mg n-3 PUFA/day; and group 2. placebo group: treated with 3 gel capsules/day containing mineral oil. Supplementation was performed for 06 months. The tissue samples and plasma were collected before and after 6 months of supplementation with n-3 PUFA. Metabolomic alterations resulting from such supplementation will be assessed from the proteomic analysis of liver tissue and plasma lipidomic analysis, both by mass spectrometry. Plasma levels of TNF-alpha and n-3 PUFA (as biomarkers of consumption) will also be evaluated. Our findings will contribute to identify and understand potential pathways of n-3 action in NASH and offer therapeutic targets for it treatment. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DOS REIS RODRIGUES OKADA, LIVIA SAMARA; OLIVEIRA, CLAUDIA P.; STEFANO, JOSE TADEU; NOGUEIRA, MONIZE AYDAR; COTRIM GUERREIRO DA SILVA, ISMAEL DALE; CORDEIRO, FERNANDA BERTUCCE; FERREIRA ALVES, VENANCIO AVANCINI; TORRINHAS, RAQUEL SUSANA; CARRILHO, FLAIR JOSE; PURI, PUNEET; et al. Omega-3 PUFA modulate lipogenesis, ER stress, and mitochondrial dysfunction markers in NASH - Proteomic and lipidomic insight. Clinical Nutrition, v. 37, n. 5, p. 1474-1484, OCT 2018. (11/09234-9, 13/03742-8)