基于“肠道菌群-Carnitine代谢-白色脂肪棕色化”途径研究苓桂术甘汤治疗肥胖症的作用机制

肥胖的大流行是全球严峻的公共卫生问题，开发疗效确切、副作用少的减肥药物有着急迫性和重要性。前期我们运用温阳化气法的代表方-苓桂术甘汤治疗肥胖症取得了良好疗效，其作用与白色脂肪棕色化的激活有关。预实验中我们发现肠道菌群参与了苓桂术甘汤对白色脂肪棕色化的调控，并鉴定出了中药相关肠道菌群及主要差异代谢产物Carnitine。多个研究已证实Carnitine可激活棕色脂肪。据此，我们推测“肠道菌群-Carnitine代谢-白色脂肪棕色化”途径是是苓桂术甘汤的减肥作用靶点。为证实这一假说，本项目拟复制肥胖小鼠模型，以伪无菌和粪菌移植小鼠做对照，借助宏基因组学、代谢组学等明确中药相关肠道菌种及差异代谢产物，筛选出具体信号通路，并用分子生物学方法验证。本研究成果将从肠道菌群-代谢产物-脂肪轴激活脂肪重塑的新角度阐释温阳化气法治疗肥胖症的作用机制，也为苓桂术甘汤治疗肥胖症的推广提供前期实验室依据。

Obosity is becoming severe worldwide public health issue because of its epidemic.It is very urgent and crucial to explore effective and safe anti-obesity drugs. As the classic decoction of Warming Yang and Activating Qi,the Lingguizhugan decoction has been used by us to treat obesity with satisfactory effects,the mechanism is related with activating the browning of White Adipose Tissue(WAT).Pre-experiments have certified that the gut microbiota plays a role in the mediating WAT browning by the Lingguizhugan decoction.We identified the relative gut microbiota of the Lingguizhugan decoction,as well as its differential metabolites-Carnitine.Several researches verified Carnitine can activating the Brown Adipose Tissue(BAT).Hereby, we infer that the pathway of gut microbiota-Carnitine metabolism-browning of WAT is the target of the Lingguizhugan decoction treating obesity.In order to confirm this hypothesis, in the project,we will replicate the obesity mice model,compare them with the pseudo-germ free mice and Fecal Microbiota Transplantation(FMT) mice, and apply the Metagenomics and Metabonomics to clarify the definite species of gut microbiota, differential metabolites and precise signal pathways mediating the WAT browning by the Lingguizhugan decoction, and verify the signal pathways by molecular biology Technology.The research results will clarify the mechanism of Warming Yang and Activating Qi treatment on obesity from a new aspect of gut microbiota-metabolites-adipose tissue axis,and provide experimental research evidences for Lingguizhugan decoction to treat obesity.