Omega-3 Fatty Acid Interventions in Liver Disease

Omega-3 polyunsaturated fatty acids (PUFAs), principally eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have attracted considerable attention as potential modulators of hepatic lipid metabolism, inflammation and fibrogenesis. In chronic liver disorders such as non-alcoholic fatty liver disease (NAFLD) and its progressive form non-alcoholic steatohepatitis (NASH), accumulation of triglycerides within hepatocytes and activation of inflammatory pathways drive the transition to fibrosis and cirrhosis. Dietary supplementation or endogenous elevation of omega-3 PUFAs has been shown to attenuate hepatosteatosis, reduce pro-inflammatory cytokine release and inhibit activation of hepatic stellate cells, the principal mediators of fibrotic matrix deposition. Mechanistic studies reveal that EPA and DHA regulate nuclear receptors and cell-surface sensors to influence gene networks controlling lipid uptake, oxidation and export, while also modulating gut microbiota composition and gut–liver signalling. Clinical trials and preclinical models jointly support a favourable safety profile and hint at improvements in surrogate markers of liver injury, though consistency of histological benefit remains under evaluation. The global burden of fatty liver disease and the absence of licensed pharmacotherapies underscore the practical appeal of omega-3 PUFA interventions as adjunctive or preventative strategies.

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Omega-3 Fatty Acid Interventions in Liver Disease publication trend

The graph below shows the total number of articles in omega-3 fatty acid interventions in liver disease across all publications each year (not limited to Nature Index journals).

Technical terms

Omega-3 polyunsaturated fatty acids (PUFAs): Dietary lipids, notably EPA and DHA, that modulate inflammation and lipid metabolism.

Non-alcoholic fatty liver disease (NAFLD): Hepatic steatosis in the absence of significant alcohol intake, often linked to metabolic syndrome.

Non-alcoholic steatohepatitis (NASH): A progressive form of NAFLD characterised by steatosis, inflammation and cell injury.

Hepatic stellate cells: Liver-resident cells that transdifferentiate into collagen-secreting myofibroblasts upon injury.

Fibrosis: Excessive accumulation of extracellular matrix proteins, leading to scar formation.

Gut–liver axis: Bidirectional communication between the intestinal environment and the liver via microbial, metabolic and immunological pathways.

Free fatty acid receptor 4 (FFAR4): A G protein-coupled receptor that senses long-chain fatty acids and influences metabolic and inflammatory signalling.

Betacellulin: An epidermal growth factor receptor ligand implicated in cell proliferation and fibrogenic activation in the liver.

References

1. Nonalcoholic Fatty Liver Disease and Omega-3 Fatty Acids: Mechanisms and Clinical Use. Annual Review of Nutrition (2023).
2. Multi‐omic network analysis identified betacellulin as a novel target of omega‐3 fatty acid attenuation of western diet‐induced nonalcoholic steatohepatitis. EMBO Molecular Medicine (2023).
3. Endogenous n-3 PUFAs Improve Non-Alcoholic Fatty Liver Disease through FFAR4-Mediated Gut–Liver Crosstalk. Nutrients (2023).