Targeting n-3 Polyunsaturated Fatty Acids in Non-Alcoholic Fatty Liver Disease
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Published:2020-09-11
Issue:31
Volume:27
Page:5250-5272
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ISSN:0929-8673
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Container-title:Current Medicinal Chemistry
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language:en
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Short-container-title:CMC
Author:
Valenzuela Rodrigo1, Ortiz Macarena2, Hernández-Rodas María Catalina1, Echeverría Francisca1, Videla Luis Alberto3
Affiliation:
1. Department of Nutrition, Faculty of Medicine, University of Chile, Av. Independencia 1027, Independencia, Santiago 8380453, Chile 2. Nutrition and Dietetics School, Faculty of Health Sciences, Catholic University of Maule, Merced 333, Curicó 3340000, Chile 3. Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Av. Independencia 1027, Independencia, Santiago 8380453, Chile
Abstract
Background:
Non-Alcoholic Fatty Liver Disease (NAFLD) is characterized by abnormal
hepatic accumulation of triacylglycerides in the absence of alcohol consumption, in association with
Oxidative Stress (OS), a pro-inflammatory state and Insulin Resistance (IR), which are attenuated by
n-3 long-chain polyunsaturated Fatty Acids (FAs) C20-C22 (LCPUFAs) supplementation. Main
causes of NAFLD comprise high caloric intake and a sedentary lifestyle, with high intakes of saturated
FAs.
Methods:
The review includes several searches considering the effects of n-3 LCPUFAs in NAFLD
in vivo and in vitro models, using the PubMed database from the National Library of Medicine-
National Institutes of Health.
Results:
The LCPUFAs eicosapentaenoic acid (C20:5 n-3, EPA) and docosahexaenoic acid (C22:6 n-
3, DHA) have a positive effect in diminishing liver steatosis, OS, and the levels of aspartate
aminotransferase, alanine aminotransferase and pro-inflammatory cytokines, with improvement of
insulin sensitivity and adiponectin levels. The molecular pathways described for n-3 LCPUFAs in
cellular and animal models and humans include peroxisome proliferator–activated receptor-α activation
favouring FA oxidation, diminution of lipogenesis due to sterol responsive element binding
protein-1c downregulation and inflammation resolution. Besides, nuclear factor erythroid-2-related
factor-2 activation is elicited by n-3 LCPUFA-derived oxidation products producing direct and indirect
antioxidant responses, with concomitant anti-fibrogenic action.
Conclusion:
The discussed effects of n-3 LCPUFA supplementation support its use in NAFLD,
although having a limited value in NASH, a contention that may involve n-3 LCPUFA oxygenated
derivatives. Clinical trials establishing optimal dosages, intervention times, type of patients and
possible synergies with other natural products are needed in future studies.
Funder
FONDECYT National Fund for Scientific and Technological Development
Publisher
Bentham Science Publishers Ltd.
Subject
Pharmacology,Molecular Medicine,Drug Discovery,Biochemistry,Organic Chemistry
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