Effect of Omega-3 Polyunsaturated Fatty Acids on Lipid Metabolism in Patients With Metabolic Syndrome and NAFLD

Václav Šmíd, Karel Dvořák, Petr Šedivý, Vít Kosek, Martin Leníček, Monika Dezortová, Jana Hajšlová, Milan Hájek, Libor Vítek, Kamila Bechyňská, Radan Brůha, Václav Šmíd, Karel Dvořák, Petr Šedivý, Vít Kosek, Martin Leníček, Monika Dezortová, Jana Hajšlová, Milan Hájek, Libor Vítek, Kamila Bechyňská, Radan Brůha

Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. n-3 polyunsaturated fatty acids (n-3-PUFAs) have been reported to ameliorate the progression of NAFLD in experimental studies; however, clinical trials have yielded contradictory results. The aim of our study was to assess the effects of n-3-PUFA administration on lipid metabolism and the progression of NAFLD in patients with metabolic syndrome. Sixty patients with metabolic syndrome and NAFLD were randomized in a double-blind placebo-controlled trial (3.6 g/day n-3-PUFA vs. placebo). During the 1-year follow-up, the patients underwent periodic clinical and laboratory examinations, liver stiffness measurements, magnetic resonance spectroscopy of the liver, and plasma lipidomic analyses. After 12 months of n-3-PUFA administration, a significant decrease in serum GGT activity was recorded compared with the placebo group (2.03 ± 2.8 vs. 1.43 ± 1.6; P < 0.05). Although no significant changes in anthropometric parameters were recorded, a significant correlation between the reduction of liver fat after 12 months of treatment-and weight reduction-was observed; furthermore, this effect was clearly potentiated by n-3-PUFA treatment (P < 0.005). In addition, n-3-PUFA treatment resulted in substantial changes in the plasma lipidome, with n-3-PUFA-enriched triacylglycerols and phospholipids being the most expressed lipid signatures. Conclusion: Twelve months of n-3-PUFA treatment of patients with NAFLD patients was associated with a significant decrease in GGT activity, the liver fat reduction in those who reduced their weight, and beneficial changes in the plasma lipid profile.

Trial registration: ClinicalTrials.gov NCT02647294.

© 2022 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.

Figures

FIG. 1
FIG. 1
Correlation between weight change and liver fat content. Correlation between weight change and liver fat content change before and after treatment in the n‐3‐PUFA group (A) and in the placebo group (B). Liver fat content reduction was potentiated by n‐3‐PUFA treatment (P = 0.0017).
FIG. 2
FIG. 2
The effect of n‐3‐PUFA administration on plasma lipidome. PCA revealed the clustering of samples into two groups based on the type and time of treatment using the UHPLC‐HRMS/MS technique. Treatment with n‐3‐PUFA resulted in a shift from the right cluster (red dots = time 0) to the left cluster (the cluster with a higher intensity of signatures of lipids containing n‐3‐PUFA).
FIG. 3
FIG. 3
The effect of n‐3‐PUFA administration on composition of plasma lipids. (A) The enrichment of plasma lipids by n‐3‐PUFA in the treated group was already proven after 3 months and remained stable until the end of the study, as described on the 40 most significant lipids by analysis of variance P value. (B) The observed changes persisted for the remainder of the study period (months 3, 6, 9, and 12) in all subjects (demonstrated on a selection of four lipids).

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