Systemic Characterization of an Obese Phenotype in the Zucker Rat Model Defining Metabolic Axes of Energy Metabolism and Host-Microbial Interactions
Systemic Characterization of an Obese Phenotype in the Zucker Rat Model Defining Metabolic Axes of Energy Metabolism and Host-Microbial Interactions
复制标题
DOI：
10.1021/acs.jproteome.6b00090
复制
发表时间：
2016-06-01
影响因子：
4.4
通讯作者：
Li, Jia V.
中科院分区：
文献类型：
--
作者：
Phetcharaburanin, Jutarop;Lees, Hannah;Li, Jia V.
Zucker(fa/fa)大鼠是一种有价值且被广泛应用于肥胖研究的动物模型。然而，肥胖的Zucker大鼠全身反应背后的代谢网络仍有待阐明。这些信息对我们进一步了解微生物或宿主微生物代谢产物的循环及其对宿主代谢的影响是重要的。采用H-1核磁共振代谢谱技术检测肥胖(fa/fa，n=12)和瘦(fa/+，n=12)Zucker大鼠门静脉、外周血浆、尿液和粪水的整体代谢差异。在瘦Zucker大鼠中，发现宿主-微生物共同代谢物的尿液浓度显著更高。与瘦体动物相比，肥胖大鼠粪便中乳酸、短链脂肪酸、3-羟基苯丙酸和甘油的浓度较高，而缬氨酸和甘氨酸的浓度较低。无论表型如何，门静脉血中SCFAs、三羧酸循环中间产物和胆碱代谢产物的浓度均高于外周血。然而，与外周血相比，门静脉血中琥珀酸、苯丙氨酸和酪氨酸的水平较高，而肥胖大鼠则没有。我们的发现表明，丙酸、醋酸盐、胆碱和三甲胺的吸收与Zucker大鼠的表型无关。然而，尿宿主-微生物共代谢产物与表型高度相关，这表明在瘦和肥胖的Zucker大鼠中存在不同的肠道微生物代谢活动。这项工作促进了我们对与肥胖相关的代谢过程的理解，特别是在肥胖背景下肠道微生物区系的代谢功能。
The Zucker (fa/fa) rat is a valuable and extensively utilized model for obesity research. However, the metabolic networks underlying the systemic response in the obese Zucker rats remain to be elucidated. This information is important to further our understanding of the circulation of the microbial or host-microbial metabolites and their impact on host metabolism. H-1 nuclear magnetic resonance spectroscopy-based metabolic profiling was used to probe global metabolic differences in portal vein and peripheral blood plasma, urine and fecal water between obese (fa/fa, n = 12) and lean (fa/+, n = 12) Zucker rats. Urinary concentrations of host-microbial co-metabolites were found to be significantly higher in lean Zucker rats. Higher concentrations of fecal lactate, short chain fatty acids (SCFAs), 3-hydroxyphenyl propionic acid and glycerol, and lower levels of valine and glycine were observed in obese rats compared with lean animals. Regardless of phenotype, concentrations of SCFAs, tricarboxylic acid cycle intermediates, and choline metabolites were higher in portal vein blood compared to peripheral blood. However, higher levels of succinate, phenylalanine and tyrosine were observed in portal vein blood compared with peripheral blood from lean rats but not in obese rats. Our findings indicate that the absorption of propionate, acetate, choline, and trimethylamine is independent of the Zucker rat phenotypes. However, urinary host-microbial co-metabolites were highly associated with phenotypes, suggesting distinct gut microbial metabolic activities in lean and obese Zucker rats. This work advances our understanding of metabolic processes associated with obesity, particularly the metabolic functionality of the gut microbiota in the context of obesity.