N-3 highly unsaturated fatty acids combined with pro-biotics or post-biotics synergistically alleviate dyslipidemia in rats exposed to chronic mild stress

Abstract

BACKGROUND/OBJECTIVES: This research is objective to examine the synergistic hypocholesterolemic effects of n-3 highly unsaturated fatty acids (HUFA) combined with pro-or post-biotics on dyslipidemia caused by chronic mild stress (CMS) through modulating biosynthesis and clearance of cholesterol. MATERIALS/METHODS: Rats were assigned into 7 random groups, each containing 8 rats: n-3 HUFA deficient diet without CMS, CMS with n-3 HUFA deficient diet, pro-biotics, post-biotics, n-3 HUFA, n-3 HUFA with pro-biotics, and n-3 HUFA with post-biotics. The induction of CMS occurred over 5 weeks during the 12-week dietary supplementation period. RESULTS: The n-3 HUFA, pro-biotics, and post-biotics 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). CONCLUSION: Therefore, n-3 HUFA with pro-biotics or post-biotics exert synergistic hypocholesterolemic effects on dyslipidemia induced by CMS through regulating biosynthesis and cholesterol clearance.