Gut dysbiosis contributes to SCFAs reduction-associated adipose tissue macrophage polarization in gestational diabetes mellitus

作者全名：Li, Hongli; Liu, Siqi; Chen, Hao; Zhou, Linwei; Chen, Bingnan; Wang, Min; Zhang, Dan; Han, Ting-Li; Zhang, Hua

作者地址：[Li, Hongli; Liu, Siqi; Chen, Hao; Zhou, Linwei; Chen, Bingnan; Wang, Min; Zhang, Dan; Zhang, Hua] Chongqing Med Univ, Affiliated Hosp 1, Dept Obstet & Gynecol, Chongqing 400016, Peoples R China; [Li, Hongli; Liu, Siqi; Chen, Hao; Zhou, Linwei; Zhang, Hua] Chongqing Med Univ, State Key Lab Maternal & Fetal Med Chongqing, Chongqing 400016, Peoples R China; [Li, Hongli] Chongqing Med Univ, Chongqing Key Lab Translat Med Major Metab Dis, Chongqing 400016, Peoples R China; [Han, Ting-Li] Chongqing Med Univ, Affiliated Hosp 2, Dept Obstet & Gynecol, Chongqing 400010, Peoples R China

通信作者：Zhang, H (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Obstet & Gynecol, Chongqing 400016, Peoples R China.; Han, TL (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Obstet & Gynecol, Chongqing 400010, Peoples R China.

来源：LIFE SCIENCES

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001247434800001

JCR分区：Q1

影响因子：5.2

年份：2024

卷号：350

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Gut microbiota; Fecal microbiota transplantation; Short -chain fatty acids; Adipose tissue; Macrophage polarization; Gestational diabetes

摘要：Aims: The prevalence of gestational diabetes mellitus (GDM) has spurred investigations into various interconnected factors, among which gut dysbiosis is notably prominent. Although gut dysbiosis is strongly associated with GDM, the specific role of the gut microbiome in the pathogenesis of GDM remains unknown. This study aims to explore the pathogenesis of GDM from gut microbiota. Materials and methods: In our study, we constructed two GDM mice models: one induced by a high-fat diet (HFD) and the other through fecal microbiota transplantation (FMT) from GDM patients. In vitro, we used a co-culture system of RAW264.7 and 3T3-L1 adipocytes. Key findings: We induced a GDM-like state in pregnant mice by FMT from GDM patients, which was consistent with the HFD model. A potential mechanism identified involves the diminished abundance of SCFA-producing microbiota, which reduces SCFAs, particularly propionic acid and butyric acid. In vitro, butyric and propionic acids were observed to alleviate LPS-induced TLR4-NF-kappa B activation, thereby reducing inflammation levels and inhibiting adipose insulin resistance via the PI3K/AKT signaling pathway. This reduction appears to trigger the polarization of adipose tissue macrophages toward M1 and promote insulin resistance in adipose tissue. Significance: Our study fills this knowledge gap by finding that alterations in gut microbiota have an independent impact on hyperglycemia and insulin resistance in the GDM state. In vivo and in vitro, gut dysbiosis is linked to adipose tissue inflammation and insulin resistance via the bacterial product SCFAs in the GDM state, providing new insights into the pathogenesis of GDM.

基金机构：National Natural Science Foundation of China [81971406, 81871185]; The 111 Project [(2016) 32]; Chongqing Science & Technology Commission [cstc2021jcyj-msxmX0213]; Chongqing Municipal Education Commission [KJZD-K202100407]; Chongqing Health Commission and Chongqing Science & Technology Commission [2021MSXM121, 2020MSXM101]; Foundation of State Key Laboratory of Ultrasound in Medicine and Engineering [2023KFKTO02]; Senior Medical Talents Program of Chongqing for Young and Middle-aged [[2022] 15]; Chongqing Graduate Research Innovation Project [CYS21218]

基金资助正文：This study was supported by the National Natural Science Foundation of China (Nos. 81971406, 81871185) , The 111 Project (Yuwaiz-huan (2016) 32) , Chongqing Science & Technology Commission (cstc2021jcyj-msxmX0213) , Chongqing Municipal Education Commission (KJZD-K202100407) , Chongqing Health Commission and Chongqing Science & Technology Commission (2021MSXM121, 2020MSXM101) , Foundation of State Key Laboratory of Ultrasound in Medicine and Engineering (2023KFKTO02) , Senior Medical Talents Program of Chongqing for Young and Middle-aged [2022] 15, and Chongqing Graduate Research Innovation Project (CYS21218) .