Published online Mar 27, 2025. doi: 10.4254/wjh.v17.i3.102286
Revised: February 20, 2025
Accepted: March 5, 2025
Published online: March 27, 2025
Processing time: 163 Days and 9.8 Hours
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.
To explore the impact of various omega-6 fatty acid subtypes on the pathogenesis and therapeutic strategies of MASLD.
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.
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.
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.
Core Tip: Dietary habits extend beyond influencing metabolic dysfunction-associated steatotic liver disease onset, serving as a fundamental component in its therapeutic management. While fats have a deleterious role in the pathogenesis of liver steatosis and fibrosis, unsaturated fats provide a crucial safeguard in metabolic dysfunction-associated steatotic liver disease management. Omega-6 polyunsaturated fat subtypes exhibit varying pro- and anti-inflammatory effects; most arachidonic acid-derived eicosanoids, exhibit pro-inflammatory effects, while linoleic acid and natural conjugated linoleic acid do not increase inflammation, even at high doses, and may even exert beneficial effects. Therefore, further research is needed to explore dietary sources of healthy omega-6 fatty acids.