Semaglutide alleviates gut microbiota dysbiosis induced by a high-fat diet

作者全名：Duan, Xinhao; Zhang, Lei; Liao, Yi; Lin, Zijing; Guo, Changxin; Luo, Sen; Wang, Fu; Zou, Zhen; Zeng, Zhijun; Chen, Chengzhi; Qiu, Jingfu

作者地址：[Duan, Xinhao; Zhang, Lei; Liao, Yi; Lin, Zijing; Guo, Changxin; Qiu, Jingfu] Chongqing Med Univ, Sch Publ Hlth, Dept Hlth Lab Technol, Chongqing 400016, Peoples R China; [Zhang, Lei] Chongqing Hlth Serv Ctr, Chongqing 400020, Peoples R China; [Luo, Sen; Wang, Fu; Zeng, Zhijun; Chen, Chengzhi] Chongqing Med Univ, Sch Publ Hlth, Dept Occupat & Environm Hlth, Chongqing 400016, Peoples R China; [Zou, Zhen] Chongqing Med Univ, Inst Life Sci, Mol Biol Lab Resp Dis, Chongqing 400016, Peoples R China; [Zeng, Zhijun; Chen, Chengzhi] Chongqing Med Univ, Res Ctr Environm & Human Hlth, Sch Publ Hlth, Chongqing 400016, Peoples R China; [Zeng, Zhijun; Chen, Chengzhi; Qiu, Jingfu] 1 Yixueyuan Rd, Chongqing 400016, Peoples R China

通信作者：Zeng, ZJ; Chen, CZ; Qiu, JF (通讯作者)，1 Yixueyuan Rd, Chongqing 400016, Peoples R China.

来源：EUROPEAN JOURNAL OF PHARMACOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001201859500001

JCR分区：Q1

影响因子：4.2

年份：2024

卷号：969

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Gut microbiota; Obesity; High-fat diet; Semaglutide; Anti-obesity drug

摘要：This study investigated the effects of semaglutide (Sema) on the gut microbiota of obese mice induced with highfat diet (HFD). Male C57BL/6 J mice aged 6 weeks were enrolled and randomly distributed to four groups, which were provided with a normal control diet (NCD,NCD + Sema) and a 60% proportion of a high-fat diet (HFD,HFD + Sema), respectively. HFD was given for 10 weeks to develop an obesity model and the intervention was lasted for 18 days. The results showed semaglutide significantly reduced body weight gain, areas under the curve (AUC) of glucose tolerance test and insulin resistance test, as well as adipose tissue weight in mice. Semaglutide effectively reduced lipid deposition and lipid droplet formation in the liver of obese mice, and regulated the expression of genes related to abnormal blood glucose regulation. Additionally, semaglutide influenced the composition of gut microbiota, mitigating the microbial dysbiosis induced by a high-fat diet by impacting the diversity of the gut microbiota. After the high-fat diet intervention, certain strains such as Akkermansia, Faecalibaculum, and Allobaculum were significantly decreased, while Lachnospiraceae and Bacteroides were significantly increased. However, the application of semaglutide restored the lost flora and suppressed excessive bacterial abundance. Moreover, semaglutide increased the content of tight junction proteins and repaired the damage to intestinal barrier function caused by the high-fat diet intervention. Furthermore, correlation analysis revealed inverse relationship among Akkermansia levels and weight gain, blood glucose levels, and various obesity indicators. Correlation analysis also showed that Akkermansia level was negatively correlated with weight gain, blood glucose levels and a range of obesity indicators. This phenomenon may explain the anti-obesity effect of semaglutide, which is linked to alterations in gut microbiota, specifically an increase in the abundance of Akkermansia. In summary, our findings indicate that semaglutide has the potential to alleviate gut microbiota dysbiosis, and the gut microbiota may contribute to the obesity-related effects of this drug.

基金机构：Natural Science Foundation of Chongqing [cstc2020jcyj-zdxmX0029]

基金资助正文：This study was supported by the key project of the Natural Science Foundation of Chongqing (cstc2020jcyj-zdxmX0029) .