Synergistic effects of pro-biotics or post-biotics with n-3 highly unsaturated fatty acids on chronic mild stress-induced dyslipidemia in rats

Abstract

This research is objective to examine the synergistic effects of pro- or post-biotics combined with n-3 highly unsaturated fatty acids (HUFA) on dyslipidemia caused by depression through modulating biosynthesis and clearance of cholesterol. Rats were assigned into 7 random groups, each containing 8 rats: n-3 HUFA deficient diet without chronic mild stress (CMS), CMS with n-3 HUFA deficient diet, pro-biotics, post-biotics, n-3 HUFA, pro-biotics and n-3 HUFA, and post-biotics and n-3 HUFA. The induction of CMS occurred over five weeks during the 12-week dietary supplementation period. The pro-biotics, post-biotics, and n-3 HUFA ameliorated dyslipidemia caused by CMS and downregulated cholesterol biosynthesis through decreasing sterol regulatory element-binding protein-2 (Biotics, P < 0.001; n3, P < 0.001; synergistic, P = 0.014) and 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (Biotics, P < 0.001; n3, P < 0.001; synergistic, P < 0.001). Moreover, they upregulated cholesterol clearance by increasing low-density lipoprotein-cholesterol reuptake through proprotein convertase subtilisin/kexin type 9 (Biotics, P < 0.001; n3, P < 0.001; synergistic, P = 0.036) and bile acids biosynthesis through cytochrome p450 family 7 subfamily A member 1 (Biotics, P < 0.001; n3, P < 0.001; synergistic, P < 0.001) and cytochrome p450 family 27 subfamily A member 1 (Biotics, P < 0.001; n3, P < 0.001; synergistic, P = 0.001). Therefore, pro-biotics or post-biotics with n-3 HUFA exert synergistic hypocholesterolemic effects on dyslipidemia induced by CMS through regulating biosynthesis and cholesterol clearance.