Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, Guangdong Province 510080, PR China; Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, Guangdong Province 510080, PR China.
Department of Obstetrics and Gynecology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province 510080, PR China.
J Nutr Biochem. 2018 Jun;56:175-182. doi: 10.1016/j.jnutbio.2018.02.011. Epub 2018 Feb 27.
Short-chain fatty acids (SCFAs), the major products of dietary fiber fermentation by intestinal microflora, exert beneficial effects on pathogenesis of multiple metabolic diseases. The aim of this study was to determine whether SCFAs from fermentation of pectin (PE), a soluble dietary fiber, prevent the development of atherosclerosis in apolipoprotein E-deficient (apoE) mice. Male apoE mice (8-week-old) were fed a high-fat, high-cholesterol diet (HCD; 21% wt/wt fat, 0.15% wt/wt cholesterol) or HCD supplemented with 20% wt/wt PE (HCD+PE) alone or with antibiotics (HCD+PE + A) in drinking water for 12 weeks. Serum lipids and SCFAs concentrations, atherosclerotic lesion area, and intestinal morphology and function were measured. Caco-2 cells were treated with SCFAs to determine whether they affected the expression of genes involved in cholesterol absorption. HCD+PE-treated mice exhibited decreased serum total and low-density lipoprotein cholesterol, and reduced atherosclerotic lesion area compared with HCD mice. These beneficial effects of PE were not observed in the HCD+PE+A group. Incubation of Caco-2 cells with butyrate, but not acetate and propionate, down-regulated the expression of Niemann-Pick C1-Like 1 but up-regulated the ATP-binding cassette transporters G5 and G8 (ABCG5 and G8) at the mRNA level. Butyrate treatment also increased transcriptional activity of liver X receptor in Caco-2 cells. Our data suggest that butyrate from PE intestinal fermentation protects mice from the progression of diet-induced atherosclerosis in apoE mice. These findings suggest a novel mechanism by which dietary fiber may prevent the development of atherosclerosis.
短链脂肪酸（SCFAs）是肠道微生物发酵膳食纤维的主要产物，对多种代谢性疾病的发病机制具有有益作用。本研究旨在确定果胶（PE）发酵产生的 SCFAs 是否可以预防载脂蛋白 E 缺陷（apoE）小鼠动脉粥样硬化的发生。雄性 apoE 小鼠（8 周龄）给予高脂肪、高胆固醇饮食（HCD；21%wt/wt 脂肪，0.15%wt/wt 胆固醇）或 HCD 补充 20%wt/wt PE（HCD+PE），单独或用抗生素（HCD+PE+A）饮水 12 周。测量血清脂质和 SCFAs 浓度、动脉粥样硬化病变面积以及肠道形态和功能。用 SCFAs 处理 Caco-2 细胞，以确定它们是否影响胆固醇吸收相关基因的表达。与 HCD 组相比，PE 处理组小鼠血清总胆固醇和低密度脂蛋白胆固醇降低，动脉粥样硬化病变面积减小。但在 HCD+PE+A 组未观察到 PE 的这些有益作用。丁酸盐孵育 Caco-2 细胞，但不是乙酸盐和丙酸盐，下调尼曼-匹克 C1 样 1 基因的表达，但上调 ATP 结合盒转运蛋白 G5 和 G8（ABCG5 和 G8）的 mRNA 水平。丁酸盐处理还增加了 Caco-2 细胞中肝 X 受体的转录活性。我们的数据表明，PE 肠道发酵产生的丁酸盐可保护 apoE 小鼠免受饮食诱导的动脉粥样硬化进展。这些发现提示了膳食纤维预防动脉粥样硬化发展的一种新机制。
