Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Mar 27;17(3):102286.
doi: 10.4254/wjh.v17.i3.102286.

Metabolic dysfunction-associated steatotic liver disease and omega-6 polyunsaturated fatty acids: Friends or foes

Mona A Hegazy  1 , Safaa M Ahmed  2 , Shaimaa M Sultan  3 , Osama F Afifi  4 , Manal A Mohamed  5 , Alshimaa E Azab  6 , Mohamed A Hassanen  7 , Rakan K Zaben  7
Affiliations

Metabolic dysfunction-associated steatotic liver disease and omega-6 polyunsaturated fatty acids: Friends or foes

Mona A Hegazy et al. World J Hepatol. .

Abstract

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide. Its prevalence is closely linked to the dramatic rise in obesity and non-communicable diseases. MASLD exhibits a progressive trajectory that may culminate in development of hepatic cirrhosis, thereby predisposing affected individuals to an elevated likelihood of hepatocarcinogenesis. Diet, especially dietary fatty acids, serves as a key link between nutrient intake and MASLD pathogenesis.

Aim: To explore the impact of various omega-6 fatty acid subtypes on the pathogenesis and therapeutic strategies of MASLD.

Methods: A systematic literature search was conducted across Web of Science, PubMed, Cochrane Central, Scopus, and Embase databases from inception through June 2024 to identify all original studies linking different subtypes of omega-6 polyunsaturated fatty acids to the pathogenesis and management of MASLD. The search strategy explored the linkage between omega-6 polyunsaturated fatty acids and their subtypes, including linoleic acid (LA), gamma-linolenic acid (GLA), arachidonic acid, conjugated LA, and docosapentaenoic acid, in relation to MASLD and cardiometabolic risk.

Results: By employing the specified search strategy, a total of 83 articles were identified as potentially eligible. During the title, abstract, and full-text screening phases, 27 duplicate records were removed, leaving 56 records for relevance screening. Of these, 43 records were excluded for reasons such as irrelevance and language restrictions (limited to English), resulting in 13 full-text articles being included for detailed assessment (10 human studies,1 animal study, and 2 review articles). Although certain subtypes, as GLA, dihomo-GLA, omega-6-derived oxylipins, and most arachidonic acid-derived eicosanoids, exhibit pro-inflammatory effects, our findings suggest that other subtypes such as LA, cis-9, trans-11 conjugated LA, and docosapentaenoic acid have beneficial effects on fatty liver, cardiometabolic risk factors, and inflammation, even at high intake levels.

Conclusion: The varying health effects of omega-6 fatty acids, ranging from anti-inflammatory to pro-inflammatory impacts on the liver, leave the question of their recommendation for MASLD patients unresolved. This underscores the importance of careful selection when considering omega-6 supplementation.

Keywords: Arachidonic acid; Conjugated linoleic acid; Eicosanoids; Lipid metabolism; Metabolic dysfunction-associated steatotic liver disease; Omega-6 polyunsaturated fatty acids; Oxidative stress; Steatohepatitis.

PubMed Disclaimer

Conflict of interest statement

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

Figures

Figure 1
Figure 1
PRISMA checklist.
Figure 2
Figure 2
Metabolism of omega-3 and omega-6 polyunsaturated fatty acids. LA: Linoleic acid; GLA: Gamma-linolenic acid; DGLA: Dihomo-gamma-linolenic acid; AA: Arachidonic acid; ALA: Alpha-linolenic acid; EPA: Eicosapentaenoic acid; DHA: Docosahexaenoic acid.
Figure 3
Figure 3
Omega-6 polyunsaturated fatty acid subtypes. ELOVL: Elongation of very long chain fatty acids.
See this image and copyright information in PMC

References

    1. Lazarus JV, Newsome PN, Francque SM, Kanwal F, Terrault NA, Rinella ME. Reply: A multi-society Delphi consensus statement on new fatty liver disease nomenclature. Hepatology. 2024;79:E93–E94. - PubMed
    1. Riazi K, Azhari H, Charette JH, Underwood FE, King JA, Afshar EE, Swain MG, Congly SE, Kaplan GG, Shaheen AA. The prevalence and incidence of NAFLD worldwide: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2022;7:851–861. - PubMed
    1. Huang DQ, El-Serag HB, Loomba R. Global epidemiology of NAFLD-related HCC: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2021;18:223–238. - PMC - PubMed
    1. Eslamparast T, Tandon P, Raman M. Dietary Composition Independent of Weight Loss in the Management of Non-Alcoholic Fatty Liver Disease. Nutrients. 2017;9:800. - PMC - PubMed
    1. Yasutake K, Nakamuta M, Shima Y, Ohyama A, Masuda K, Haruta N, Fujino T, Aoyagi Y, Fukuizumi K, Yoshimoto T, Takemoto R, Miyahara T, Harada N, Hayata F, Nakashima M, Enjoji M. Nutritional investigation of non-obese patients with non-alcoholic fatty liver disease: the significance of dietary cholesterol. Scand J Gastroenterol. 2009;44:471–477. - PubMed

LinkOut - more resources