Dietary omega-3 polyunsaturated fatty acids relate to lower liver lipids and adipose-tissue insulin resistance, modulated by fatty acid desaturase 1 rs174546 in type 2 diabetes

Background & aims: Type 2 diabetes and metabolic dysfunction-associated steatotic liver disease (MASLD) frequently coexist and increase cardiovascular risk. Although habitual omega-3 (omega 3) polyunsaturated fatty acids (PUFAs) may improve cardiovascular risk, their metabolic effects in type 2 diabetes and MASLD remain unclear. We hypothesized that omega 3-PUFA intake reduces hepatocellular lipid content (HCL) in individuals carrying single-nucleotide polymorphisms (SNPs) of the fatty acid desaturase (FADS) 1 and FADS2 genes, which associate with higher desaturase activity. Methods: We cross-sectionally analyzed 154 participants with recent-onset type 2 diabetes from the German Diabetes Study (GDS). HCL was measured using 1H-magnetic resonance spectroscopy and omega 3-PUFA intake was assessed using semiquantitative food-frequency questionnaires. The cohort was divided into lower-and higher-omega 3-PUFA groups according to median omega 3-PUFA intake. Nine SNPs in FADS1 and FADS2 were genotyped using real-time PCR-based allelic discrimination. Results: The higher-o3-PUFA group featured lower HCL (6.9 +/- 7.1% vs. 10.5 +/- 9.1%, p= 0.01) and lower MASLD prevalence (49% vs. 65%, p= 0.05) than the lower-o3-PUFA group. Adjusted multivariable regression analyses identified negative associations of o3-PUFA intake with adipose-tissue insulin resistance, glycemia and cholesterol. The rs174546 SNP in FADS1 interacted with o3-PUFA intake on HCL (p= 0.05). Among T allele carriers of rs174546, higher o3-PUFA intake was associated with lower HCL (p =-2.60, p= 0.03). Conclusions: Adequate habitual o3-PUFA intake may reduce HCL in recent-onset type 2 diabetes, but-contrasting our hypothesis-in those carrying the T allele of rs174546, which is linked to lower desaturase activity. This highlights the impact of gene-lifestyle interaction for managing MASLD in type 2 diabetes. (c) 2026 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).