DHA and EPA improve liver IR in HFD-induced IR mice through modulating the gut microbiotas-LPS-liver axis

Previous studies have reported that docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) improved insulin resistance (IR) owing to their anti-inflammatory and lipid-lowering effects. In the study, dietary supplementation with 4% DHA or EPA both improved liver IR in high-fat diet (HFD) induced IR mice through inhibiting hepatic steatosis and activating PI3K/Akt signaling pathway, and DHA was more effective. DHA and EPA both reduced liver inflammation by inhibiting TLR4/NF-kB signaling activation, and DHA had a stronger effect. DHA and EPA decreased serum lipopolysaccharide (LPS, a metabolite of gut microbiotas) and differentially regulated the expression of LPS receptors in the liver, while DHA was more effective. In addition, DHA and EPA improved gut microbiotas through increasing the species abundance and diversity, reducing pro-inflammatory bacteria (such as Streptococcaceae) and increasing beneficial bacteria differently (such as Bifidobacterium). In conclusion, DHA and EPA improve liver IR possibly through modulating the gut microbiotas-LPS-liver axis.