Targeting n-3 Polyunsaturated Fatty Acids in Non-alcoholic Fatty Liver Disease

(E-pub Ahead of Print)

Author(s): Rodrigo Valenzuela*, Macarena Ortiz, María Catalina Hernández-Rodas, Francisca Echeverría, Luis A. Videla.

Journal Name: Current Medicinal Chemistry

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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.

Result: 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 antifibrogenic 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.

Keywords: Liver steatosis, n-3 polyunsaturated fatty acids, α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, anti-lipogenic mechanism

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Article Details

(E-pub Ahead of Print)
DOI: 10.2174/0929867326666190410121716
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