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 (ω3) polyunsaturated fatty acids (PUFAs) may improve cardiovascular risk, their metabolic effects in type 2 diabetes and MASLD remain unclear. We hypothesized that ω3-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 ω3-PUFA intake was assessed using semiquantitative food-frequency questionnaires. The cohort was divided into lower- and higher-ω3-PUFA groups according to median ω3-PUFA intake. Nine SNPs in FADS1 and FADS2 were genotyped using real-time PCR-based allelic discrimination.

RESULTS

The higher-ω3-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-ω3-PUFA group. Adjusted multivariable regression analyses identified negative associations of ω3-PUFA intake with adipose-tissue insulin resistance, glycemia and cholesterol. The rs174546 SNP in FADS1 interacted with ω3-PUFA intake on HCL (p= 0.05). Among T allele carriers of rs174546, higher ω3-PUFA intake was associated with lower HCL (β = -2.60, p= 0.03).

CONCLUSIONS

Adequate habitual ω3-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.