- Book学术

发布求助

文献互助智能选刊最新文献

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences Pub Date : 2024-12-13 DOI:10.1016/j.lfs.2024.123310

Flavia Maria Silva-Veiga, Thatiany Souza Marinho, Vanessa de Souza-Mello, Marcia Barbosa Aguila, Carlos Alberto Mandarim-de-Lacerda

{"title":"Tirzepatide, a dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), positively impacts the altered microbiota of obese, diabetic, ovariectomized mice.","authors":"Flavia Maria Silva-Veiga, Thatiany Souza Marinho, Vanessa de Souza-Mello, Marcia Barbosa Aguila, Carlos Alberto Mandarim-de-Lacerda","doi":"10.1016/j.lfs.2024.123310","DOIUrl":null,"url":null,"abstract":"<p><p>The study aimed to verify the effect of Tirzepatide (Tzp, a dual agonist GIP/GLP-1) on intestinal health and microbiota balance in an obese diabetic ovariectomized (Ovx) mice model. Female C57BL/6 mice with Ovx and diet-induced obesity with diabetes were treated with Tzp (10 nmol/kg) for four weeks. Control (C) and obese-diabetic subgroups (Od) were formed (group abbreviations: O, Ovx; T, Tzp; n = 30/group): C, CT, CO, COT, Od, OdT, OdO, OdOT. The ileum was structurally and molecularly studied, and cecal feces had microbial DNA determined. Tzp improved the intestinal barrier structure and protection. Cldn12 (Claudin 12) increased, and Muc2 (Mucin 2) decreased. JamA (junctional adhesion molecules) and Ocln (Occludin) increased. Tzp mitigated macrophage activation and inflammation, altered composition, and the contribution to microbiota: Firmicutes decreased, and Bacteroidetes increased, changing the Firmicutes / Bacteroidetes ratio. Proteobacteria, Actinobacteria, Bifidobacterium, and Clostridium increased. In addition, Bacteroides, Prevotella, and Akkermansia increased. PCA indicated a significant action of Cd14, Muc2, and Tlr4 on CO and Il17 on OdO; Il10, Cd206, Cd12, Ocln, and JamA in Od. Bacteroides, Bifidobacterium, Clostridium, Actinobacteria, and Bacteroides were enhanced in CT and COT, Provotella, Proteobacteria, and Firmicutes in CO, Od, OdT, OdO, and Akkermansia in OdOT. In conclusion, the intestinal barrier function in our model is compromised by alterations in phylogenetic diversity and intestinal microbiota, which characterize dysbiosis and potentially enable the influx of toxins into other tissues. Treatment with Tzp demonstrated the ability to reverse intestinal dysbiosis, help repair intestinal barrier integrity, and mitigate possible endotoxemia through anti-inflammatory signaling pathways.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123310"},"PeriodicalIF":5.2000,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Life sciences","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.lfs.2024.123310","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}

引用次数: 0

摘要

该研究旨在验证替扎帕肽（Tzp，一种 GIP/GLP-1 双激动剂）对肥胖糖尿病卵巢切除（Ovx）小鼠模型的肠道健康和微生物群平衡的影响。用 Tzp（10 nmol/kg）治疗卵巢切除和饮食诱发肥胖伴糖尿病的雌性 C57BL/6 小鼠四周。组成对照组（C）和肥胖糖尿病亚组（Od）（组缩写：O，Ovx；T，Tzp；n = 30/组）：C、CT、CO、COT、Od、OdT、OdO、OdOT。对回肠进行了结构和分子研究，对盲肠粪便进行了微生物 DNA 测定。Tzp改善了肠道屏障的结构和保护作用。Cldn12（Claudin 12）增加，Muc2（Mucin 2）减少。JamA（连接粘附分子）和 Ocln（Occludin）增加。Tzp 可减轻巨噬细胞的活化和炎症，改变微生物群的组成和贡献：固着菌减少，类杆菌增加，改变了固着菌/类杆菌的比例。蛋白菌、放线菌、双歧杆菌和梭状芽孢杆菌有所增加。此外，乳杆菌（Bacteroides）、普雷沃特氏菌（Prevotella）和阿克曼氏菌（Akkermansia）也有所增加。PCA 表明，Cd14、Muc2 和 Tlr4 对 CO 有显著作用，Il17 对 OdO 有显著作用；Il10、Cd206、Cd12、Ocln 和 JamA 对 Od 有显著作用。CT和COT中的乳杆菌、双歧杆菌、梭状芽胞杆菌、放线菌和乳杆菌增强，CO、Od、OdT、OdO中的普罗旺斯菌、蛋白菌和固缩菌增强，OdOT中的Akkermansia增强。总之，在我们的模型中，肠道屏障功能因系统发育多样性和肠道微生物群的改变而受到损害，这是菌群失调的特征，有可能使毒素流入其他组织。用 Tzp 治疗证明能够逆转肠道菌群失调，帮助修复肠道屏障完整性，并通过抗炎信号通路减轻可能的内毒素血症。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

Tirzepatide, a dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), positively impacts the altered microbiota of obese, diabetic, ovariectomized mice.

The study aimed to verify the effect of Tirzepatide (Tzp, a dual agonist GIP/GLP-1) on intestinal health and microbiota balance in an obese diabetic ovariectomized (Ovx) mice model. Female C57BL/6 mice with Ovx and diet-induced obesity with diabetes were treated with Tzp (10 nmol/kg) for four weeks. Control (C) and obese-diabetic subgroups (Od) were formed (group abbreviations: O, Ovx; T, Tzp; n = 30/group): C, CT, CO, COT, Od, OdT, OdO, OdOT. The ileum was structurally and molecularly studied, and cecal feces had microbial DNA determined. Tzp improved the intestinal barrier structure and protection. Cldn12 (Claudin 12) increased, and Muc2 (Mucin 2) decreased. JamA (junctional adhesion molecules) and Ocln (Occludin) increased. Tzp mitigated macrophage activation and inflammation, altered composition, and the contribution to microbiota: Firmicutes decreased, and Bacteroidetes increased, changing the Firmicutes / Bacteroidetes ratio. Proteobacteria, Actinobacteria, Bifidobacterium, and Clostridium increased. In addition, Bacteroides, Prevotella, and Akkermansia increased. PCA indicated a significant action of Cd14, Muc2, and Tlr4 on CO and Il17 on OdO; Il10, Cd206, Cd12, Ocln, and JamA in Od. Bacteroides, Bifidobacterium, Clostridium, Actinobacteria, and Bacteroides were enhanced in CT and COT, Provotella, Proteobacteria, and Firmicutes in CO, Od, OdT, OdO, and Akkermansia in OdOT. In conclusion, the intestinal barrier function in our model is compromised by alterations in phylogenetic diversity and intestinal microbiota, which characterize dysbiosis and potentially enable the influx of toxins into other tissues. Treatment with Tzp demonstrated the ability to reverse intestinal dysbiosis, help repair intestinal barrier integrity, and mitigate possible endotoxemia through anti-inflammatory signaling pathways.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

期刊介绍： Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.