Department of Pharmacology, Faculty of Pharmacy, Gazi University, Ankara, Turkey.
Department of Pharmacology, Faculty of Pharmacy, Gazi University, Ankara, Turkey.
Food Res Int. 2021 May;143:110287. doi: 10.1016/j.foodres.2021.110287. Epub 2021 Mar 9.
Excess intake of fructose may contribute to the high prevalence of metabolic disorder. In this study, we investigated the effects of kefir supplementation on the intestine-liver-adipose tissue axis in metabolic disorder induced by high-fructose diet in rats to describe mechanistic action and potential therapeutic value of kefir. Fructose was given to the rats as a 20% solution in drinking water for 15 weeks. Kefir was administrated by gastric gavage once a day during the final six weeks. Kefir supplementation improved metabolic parameters, including plasma triglyceride and insulin levels; hepatic weight, triglyceride content and fatty degeneration; omental fat mass in fructose-fed rats. Kefir supplementation decreased the ratio of Firmicutes/Bacteroidetes in feces, as well as necrotic degeneration, expression levels of nuclear factor-kappa B (NF-κB), and inducible nitric oxide synthase (iNOS), but increased expression of tight-junction proteins occludin and claudin-1, in the ileum of the fructose-fed rats. Kefir treatment also reduced the mRNA levels of key lipogenic genes sterol regulatory element-binding protein (SREBP-1c) and fatty acid synthase (FASN) together with a decline in expression of tumor necrosis factor-alpha (TNF-α), NF-κB, and glycosylated glycoprotein (CD68) in the liver. Moreover, kefir treatment improved insulin signaling at the level of insulin receptor substrate 1 (IRS-1) and phospho-endothelial nitric oxide synthase (peNOS) as well as fructose transporters (GLUT2 and GLUT5) in the liver, but not in the adipose tissue, of high-fructose-fed rats. Consequently, kefir supplementation suppresses hepatic lipogenesis and inflammatory status, but promotes insulin signaling, in association with a change of the fecal microbiota and attenuation of the intestinal permeability factors in high-fructose-fed rats. Thus, we propose that kefir has favorable effects on the hepatic and intestinal irregularities induced by fructose overconsumption.
过量摄入果糖可能是代谢紊乱高发的原因之一。在这项研究中，我们研究了在果糖饮食诱导的代谢紊乱大鼠模型中，补充开菲尔对肠-肝-脂肪组织轴的影响，以描述开菲尔的作用机制和潜在的治疗价值。在 15 周的时间里，通过给大鼠饮用 20%的果糖溶液来喂养果糖。在最后六周，通过胃管每天给大鼠一次开菲尔。开菲尔的补充改善了代谢参数，包括血浆甘油三酯和胰岛素水平；肝重、甘油三酯含量和脂肪变性；果糖喂养大鼠的网膜脂肪质量。开菲尔的补充降低了粪便中厚壁菌门/拟杆菌门的比例，以及坏死变性、核因子-κB（NF-κB）和诱导型一氧化氮合酶（iNOS）的表达水平，但增加了紧密连接蛋白闭合蛋白和 Claudin-1 的表达，在果糖喂养大鼠的回肠中。开菲尔处理还降低了关键脂肪生成基因固醇调节元件结合蛋白-1c（SREBP-1c）和脂肪酸合酶（FASN）的 mRNA 水平，同时降低了肿瘤坏死因子-α（TNF-α）、NF-κB 和糖基化糖蛋白（CD68）的表达，在肝脏中。此外，开菲尔处理改善了胰岛素受体底物 1（IRS-1）和磷酸化内皮型一氧化氮合酶（peNOS）以及果糖转运蛋白（GLUT2 和 GLUT5）在肝脏中的胰岛素信号，但在脂肪组织中没有，在高果糖喂养的大鼠中。因此，开菲尔补充抑制肝内脂肪生成和炎症状态，但促进胰岛素信号，与粪便微生物群的变化和肠通透性因子的衰减有关在高果糖喂养的大鼠中。因此，我们提出开菲尔对果糖过量摄入引起的肝肠异常有良好的作用。
