Oligomeric procyanidins combined with Parabacteroides distasonis ameliorate high-fat diet-induced atherosclerosis by regulating lipid metabolism, inflammation reaction and bile acid metabolism in ApoE−/− mice
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引用次数: 0
Abstract
Atherosclerosis (AS) is the main pathological basis of cardiovascular diseases. Hence, the prevention and treatment strategies of AS have attracted great research attention. As a potential probiotic, Pararabacteroides distasonis has a positive regulatory effect on lipid metabolism and bile acids (BAs) profile. Oligomeric procyanidins have been confirmed to be conducive to the prevention and treatment of AS, whose anti-atherosclerotic effect may be associated with the promotion of gut probiotics. However, it remains unclear whether and how oligomeric procyanidins and P. distasonis combined (PPC) treatment can effectively alleviate high-fat diet (HFD)-induced AS. In this study, PPC treatment was found to significantly decrease atherosclerotic lesion, as well as alleviate the lipid metabolism disorder, inflammation and oxidative stress injury in ApoE−/− mice. Surprisingly, targeted metabolomics demonstrated that PPC intervention altered the BA profile in mice by regulating the ratio of secondary BAs to primary BAs, and increased fecal BAs excretion. Further, quantitative polymerase chain reaction (qPCR) analysis showed that PPC intervention facilitated reverse cholesterol transport by upregulating Srb1 expression; In addition, PPC intervention promoted BA synthesis from cholesterol in liver by upregulating Cyp7a1 expression via suppression of the farnesoid X receptor (FXR) pathway, thus exhibiting a significant serum cholesterol-lowering effect. In summary, PPC attenuated HFD-induced AS in ApoE−/− mice, which provides new insights into the design of novel and efficient anti-atherosclerotic strategies to prevent AS based on probiotics and prebiotics.
动脉粥样硬化(AS)是心血管疾病的主要病理基础。因此,动脉粥样硬化的预防和治疗策略备受研究关注。作为一种潜在的益生菌,Pararabacteroides distasonis 对脂质代谢和胆汁酸(BAs)具有积极的调节作用。寡聚原花青素已被证实有利于强直性脊柱炎的预防和治疗,其抗动脉粥样硬化作用可能与肠道益生菌的促进作用有关。然而,低聚原花青素和P. distasonis(PPC)联合治疗是否能有效缓解高脂饮食(HFD)诱导的强直性脊柱炎,以及如何缓解,目前仍不清楚。本研究发现,PPC治疗可显著减少动脉粥样硬化病变,并缓解载脂蛋白E/-小鼠的脂质代谢紊乱、炎症和氧化应激损伤。令人惊讶的是,靶向代谢组学研究表明,PPC 通过调节次生 BA 与原生 BA 的比例,改变了小鼠体内 BA 的分布,并增加了粪便中 BA 的排泄量。此外,定量聚合酶链反应(qPCR)分析表明,PPC干预通过上调Srb1的表达,促进了胆固醇的逆向转运;PPC干预还通过抑制类雌激素X受体(FXR)通路,上调Cyp7a1的表达,促进了肝脏中胆固醇合成BA,因此具有显著的降低血清胆固醇的作用。总之,PPC可减轻HFD诱导的载脂蛋白E-/-小鼠强直性脊柱炎,这为设计基于益生菌和益生元的新型高效抗动脉粥样硬化策略以预防强直性脊柱炎提供了新的思路。
期刊介绍:
Food Science and Human Wellness is an international peer-reviewed journal that provides a forum for the dissemination of the latest scientific results in food science, nutriology, immunology and cross-field research. Articles must present information that is novel, has high impact and interest, and is of high scientific quality. By their effort, it has been developed to promote the public awareness on diet, advocate healthy diet, reduce the harm caused by unreasonable dietary habit, and directs healthy food development for food industrial producers.