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

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: group 1, 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. Our findings will contribute to identify and understand potential pathways of n-3 action in NASH and offer therapeutic targets for it treatment. (AU)