人类肠道常驻菌Akkermansia muciniphila对白色脂肪棕色化及能量代谢的作用研究

Both gut microbiota and browning play important roles in the development of obesity. However, the relation between gut flora and browning as well as the mechanism in metabolism regulation are still unclear. Our previous study demonstrated that Akkermansia municiphila supplementation attenuates body weight gain and fat mass in mice fed chow diet, meanwhile, the expression levels of genes involved in browning are increased in inguinal adipose tissue, suggesting that A. municiphila could induce white-to-brown fat switch, thereby improving metabolic phenotypes. Besides, the effect of A. muciniphila may depend on its outer membrane protein-Amuc_1100 according to a recent study. In this study, we will compare the.impact on white-to brown fat switch and metabolism by A. muciniphila, Amuc_1100 supplementation and the vehicle to explore the association between A. municiphila and browning as well as the underlying mechanisms. Moreover, UCP1 knockout mice are used to prove that A. municiphila improves energy metabolism by promoting browning of white adipose tissue. And we will use metabolomics to detect the plasma and urine samples, finding the different metabolites and analyzing the underlying mechanism, exploring the association between specific metabolites and.white-to-brown fat switch. Altogether, our study will provide a new candidate for the therapy of obesity and related metabolic disorders.

肠道菌群与棕色化在肥胖发生中扮演重要角色。然而肠道菌群与棕色化的关系及其调节代谢的机制尚不明确。既往研究发现人类肠道常驻菌Akkermansia muciniphila可以改善正常饮食小鼠的体重增加百分比,体脂含量,上调小鼠皮下脂肪组织棕色化相关基因的表达, 提示A. muciniphila可能通过促进棕色化进而改善体重等代谢表型。同时,近期研究提示其改善代谢的作用主要依赖外膜蛋白Amuc_1100。为明确A. muciniphila对棕色化过程及能量代谢的调节作用及其潜在机制,我们将从体内、体外水平比较A. muciniphila,Amuc_1100处理组和对照组的白色脂肪棕色化过程及能量代谢,利用UCP1基因敲除小鼠证明A. muciniphila通过影响白色脂肪棕色化进而影响能量代谢,通过代谢组学分析探索潜在机制,建立代谢物与棕色化的联系,为肥胖的干预研究提供重要靶点。

肠道菌群在肥胖发生中扮演重要角色。既往研究发现人类肠道常驻菌Akkermansia muciniphila可以改善正常饮食小鼠的体重增加百分比，体脂含量，上调小鼠皮下脂肪组织棕色化相关基因的表达。本研究在多个小鼠动物模型中，包括高脂饮食诱导肥胖小鼠以及糖尿病模型小鼠等，验证了阿克曼氏菌改善代谢异常小鼠的糖脂代谢的作用。课题组进一步探究，在现有减重降糖效果较好的药物基础上，应用阿克曼氏菌是否可以放大其改善能量代谢的作用及其机制，发现其作用可能部分通过促进脂质分解，减少脂肪组织炎症实现。最后，在小鼠模型中，发现阿克曼氏菌可能通过增强肠粘膜的线粒体活动进而改变肠道的生理状态和功能，同时通过免疫炎症状态的改善共同增强肠道屏障。