PDF(Pubmed)
Abstract：
We previously showed that Fmo5 -/- mice exhibit a lean phenotype and slower metabolic ageing. Their characteristics include lower plasma glucose and cholesterol, greater glucose tolerance and insulin sensitivity, and a reduction in age-related weight gain and whole-body fat deposition. In this paper, nuclear magnetic resonance (NMR) spectroscopy-based metabolite analyses of the urine of Fmo5 -/- and wild-type mice identified two isomers of 2,3-butanediol as discriminating urinary biomarkers of Fmo5 -/- mice. Antibiotic-treatment of Fmo5 -/- mice increased plasma cholesterol concentration and substantially reduced urinary excretion of 2,3-butanediol isomers, indicating that the gut microbiome contributed to the lower plasma cholesterol of Fmo5 -/- mice, and that 2,3-butanediol is microbially derived. Short- and long-term treatment of wild-type mice with a 2,3-butanediol isomer mix decreased plasma cholesterol and epididymal fat deposition but had no effect on plasma concentrations of glucose or insulin, or on body weight. In the case of long-term treatment, the effects were maintained after withdrawal of 2,3-butanediol. Short-, but not long-term treatment, also decreased plasma concentrations of triglycerides and non-esterified fatty acids. Fecal transplant from Fmo5 -/- to wild-type mice had no effect on plasma cholesterol, and 2,3-butanediol was not detected in the urine of recipient mice, suggesting that the microbiota of the large intestine was not the source of 2,3-butanediol. However, 2,3-butanediol was detected in the stomach of Fmo5 -/- mice, which was enriched for Lactobacillus genera, known to produce 2,3-butanediol. Our results indicate a microbial contribution to the phenotypic characteristic of Fmo5 -/- mice of decreased plasma cholesterol and identify 2,3-butanediol as a potential agent for lowering plasma cholesterol.
摘要：
我们先前表明Fmo5-/-小鼠表现出瘦表型和较慢的代谢老化。它们的特点包括降低血浆葡萄糖和胆固醇，更高的葡萄糖耐量和胰岛素敏感性，与年龄相关的体重增加和全身脂肪沉积的减少。在本文中,对Fmo5-/-和野生型小鼠的尿液进行基于核磁共振（NMR）光谱的代谢物分析，确定了2,3-丁二醇的两种异构体可区分Fmo5-/-小鼠的尿液生物标志物。Fmo5-/-小鼠的抗生素治疗增加了血浆胆固醇浓度，并大大减少了2,3-丁二醇异构体的尿排泄，表明肠道微生物组有助于降低Fmo5-/-小鼠的血浆胆固醇，2,3-丁二醇是微生物来源的。使用2,3-丁二醇异构体混合物对野生型小鼠进行短期和长期治疗可降低血浆胆固醇和附睾脂肪沉积，但对血浆葡萄糖或胰岛素浓度无影响。或体重。在长期治疗的情况下，停药2,3-丁二醇后效果得以维持.短-,但不是长期治疗，还降低了血浆中甘油三酯和非酯化脂肪酸的浓度。从Fmo5-/-到野生型小鼠的粪便移植对血浆胆固醇没有影响，和2,3-丁二醇在受体小鼠的尿液中没有检测到，这表明大肠的微生物群不是2,3-丁二醇的来源。然而,在Fmo5-/-小鼠的胃中检测到2,3-丁二醇，富含乳杆菌属，已知产生2,3-丁二醇。我们的结果表明，微生物对降低血浆胆固醇的Fmo5-/-小鼠的表型特征有贡献，并确定2,3-丁二醇是降低血浆胆固醇的潜在药物。
