• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

2 型糖尿病中微生物群和脂肪细胞线粒体损伤与 MMP12+巨噬细胞有关。

Microbiota and adipocyte mitochondrial damage in type 2 diabetes are linked by Mmp12+ macrophages.

机构信息

Carlson College of Veterinary Medicine, Oregon State University, Corvallis, OR.

Shanghai Mengniu Biotechnology R&D Co., Ltd., Shanghai, China.

出版信息

J Exp Med. 2022 Jul 4;219(7). doi: 10.1084/jem.20220017. Epub 2022 Jun 3.

DOI:10.1084/jem.20220017
PMID:35657352
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9170383/
Abstract

Microbiota contribute to the induction of type 2 diabetes by high-fat/high-sugar (HFHS) diet, but which organs/pathways are impacted by microbiota remain unknown. Using multiorgan network and transkingdom analyses, we found that microbiota-dependent impairment of OXPHOS/mitochondria in white adipose tissue (WAT) plays a primary role in regulating systemic glucose metabolism. The follow-up analysis established that Mmp12+ macrophages link microbiota-dependent inflammation and OXPHOS damage in WAT. Moreover, the molecular signature of Mmp12+ macrophages in WAT was associated with insulin resistance in obese patients. Next, we tested the functional effects of MMP12 and found that Mmp12 genetic deficiency or MMP12 inhibition improved glucose metabolism in conventional, but not in germ-free mice. MMP12 treatment induced insulin resistance in adipocytes. TLR2-ligands present in Oscillibacter valericigenes bacteria, which are expanded by HFHS, induce Mmp12 in WAT macrophages in a MYD88-ATF3-dependent manner. Thus, HFHS induces Mmp12+ macrophages and MMP12, representing a microbiota-dependent bridge between inflammation and mitochondrial damage in WAT and causing insulin resistance.

摘要

微生物组通过高脂肪/高糖（HFHS）饮食促进 2 型糖尿病的发生，但微生物组影响哪些器官/途径尚不清楚。通过多器官网络和跨物种分析，我们发现微生物依赖性的白色脂肪组织（WAT）氧化磷酸化/线粒体损伤在调节全身葡萄糖代谢中起主要作用。后续分析确定，Mmp12+巨噬细胞将微生物依赖性炎症与 WAT 中的氧化磷酸化损伤联系起来。此外，WAT 中 Mmp12+巨噬细胞的分子特征与肥胖患者的胰岛素抵抗有关。接下来，我们测试了 MMP12 的功能效应，发现 Mmp12 基因缺失或 MMP12 抑制可改善常规而非无菌小鼠的葡萄糖代谢。MMP12 处理可诱导脂肪细胞发生胰岛素抵抗。HFHS 扩增的 Oscillibacter valericigenes 细菌中存在的 TLR2 配体以 MYD88-ATF3 依赖的方式诱导 WAT 巨噬细胞中 Mmp12 的表达。因此，HFHS 诱导 Mmp12+巨噬细胞和 MMP12，代表了 WAT 中炎症和线粒体损伤之间的一种微生物依赖性桥梁，并导致胰岛素抵抗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff0/9170383/c888e76ff377/JEM_20220017_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff0/9170383/575b369849f3/JEM_20220017_GA.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff0/9170383/2bb12b653a31/JEM_20220017_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff0/9170383/7d7bd5bad760/JEM_20220017_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff0/9170383/394a81deb190/JEM_20220017_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff0/9170383/62171369110d/JEM_20220017_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff0/9170383/6ed26121c0fa/JEM_20220017_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff0/9170383/7605c696797e/JEM_20220017_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff0/9170383/ca1f1933f8f5/JEM_20220017_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff0/9170383/114cdb39d8c6/JEM_20220017_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff0/9170383/316e763c52f2/JEM_20220017_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff0/9170383/27a85aa18721/JEM_20220017_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff0/9170383/0cd837889f63/JEM_20220017_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff0/9170383/6d31bb2b1315/JEM_20220017_FigS5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff0/9170383/c888e76ff377/JEM_20220017_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff0/9170383/575b369849f3/JEM_20220017_GA.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff0/9170383/2bb12b653a31/JEM_20220017_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff0/9170383/7d7bd5bad760/JEM_20220017_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff0/9170383/394a81deb190/JEM_20220017_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff0/9170383/62171369110d/JEM_20220017_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff0/9170383/6ed26121c0fa/JEM_20220017_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff0/9170383/7605c696797e/JEM_20220017_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff0/9170383/ca1f1933f8f5/JEM_20220017_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff0/9170383/114cdb39d8c6/JEM_20220017_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff0/9170383/316e763c52f2/JEM_20220017_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff0/9170383/27a85aa18721/JEM_20220017_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff0/9170383/0cd837889f63/JEM_20220017_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff0/9170383/6d31bb2b1315/JEM_20220017_FigS5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff0/9170383/c888e76ff377/JEM_20220017_Fig8.jpg

相似文献

1
Microbiota and adipocyte mitochondrial damage in type 2 diabetes are linked by Mmp12+ macrophages.2 型糖尿病中微生物群和脂肪细胞线粒体损伤与 MMP12+巨噬细胞有关。
J Exp Med. 2022 Jul 4;219(7). doi: 10.1084/jem.20220017. Epub 2022 Jun 3.
2
Macrophage metalloelastase (MMP12) regulates adipose tissue expansion, insulin sensitivity, and expression of inducible nitric oxide synthase.巨噬细胞金属弹性蛋白酶（MMP12）调节脂肪组织扩张、胰岛素敏感性以及诱导型一氧化氮合酶的表达。
Endocrinology. 2014 Sep;155(9):3409-20. doi: 10.1210/en.2014-1037. Epub 2014 Jun 10.
3
Adipocyte inducible 6-phosphofructo-2-kinase suppresses adipose tissue inflammation and promotes macrophage anti-inflammatory activation.脂肪细胞诱导型 6-磷酸果糖-2-激酶可抑制脂肪组织炎症，并促进巨噬细胞抗炎激活。
J Nutr Biochem. 2021 Sep;95:108764. doi: 10.1016/j.jnutbio.2021.108764. Epub 2021 May 6.
4
SGLT2 Inhibition by Empagliflozin Promotes Fat Utilization and Browning and Attenuates Inflammation and Insulin Resistance by Polarizing M2 Macrophages in Diet-induced Obese Mice.恩格列净通过促进脂肪利用和棕色化以及通过极化 M2 巨噬细胞来减轻炎症和胰岛素抵抗，从而抑制 SGLT2。在饮食诱导肥胖的小鼠中。
EBioMedicine. 2017 Jun;20:137-149. doi: 10.1016/j.ebiom.2017.05.028. Epub 2017 May 26.
5
Modulation of adipose inflammation by cellular retinoic acid-binding protein 1.细胞视黄酸结合蛋白 1 对脂肪炎症的调节作用。
Int J Obes (Lond). 2022 Oct;46(10):1759-1769. doi: 10.1038/s41366-022-01175-3. Epub 2022 Jul 6.
6
MiR-130b promotes obesity associated adipose tissue inflammation and insulin resistance in diabetes mice through alleviating M2 macrophage polarization via repression of PPAR-γ.微小RNA-130b通过抑制过氧化物酶体增殖物激活受体γ来减轻M2巨噬细胞极化，从而促进糖尿病小鼠肥胖相关的脂肪组织炎症和胰岛素抵抗。
Immunol Lett. 2016 Dec;180:1-8. doi: 10.1016/j.imlet.2016.10.004. Epub 2016 Oct 13.
7
Suppressing adipocyte inflammation promotes insulin resistance in mice.抑制脂肪细胞炎症可促进小鼠胰岛素抵抗。
Mol Metab. 2020 Sep;39:101010. doi: 10.1016/j.molmet.2020.101010. Epub 2020 May 11.
8
Insulin-sensitizing effects of vitamin D repletion mediated by adipocyte vitamin D receptor: Studies in humans and mice.维生素 D 补充剂通过脂肪细胞维生素 D 受体介导的胰岛素增敏作用：在人类和小鼠中的研究。
Mol Metab. 2020 Dec;42:101095. doi: 10.1016/j.molmet.2020.101095. Epub 2020 Oct 10.
9
Adipocyte integrin-linked kinase plays a key role in the development of diet-induced adipose insulin resistance in male mice.脂肪细胞整合素连接激酶在雄性小鼠饮食诱导的脂肪胰岛素抵抗的发展中起关键作用。
Mol Metab. 2021 Jul;49:101197. doi: 10.1016/j.molmet.2021.101197. Epub 2021 Feb 26.
10
Adipocyte-specific disruption of fat-specific protein 27 causes hepatosteatosis and insulin resistance in high-fat diet-fed mice.脂肪特异性蛋白27在脂肪细胞中的特异性缺失会导致高脂饮食喂养小鼠出现肝脂肪变性和胰岛素抵抗。
J Biol Chem. 2015 Jan 30;290(5):3092-105. doi: 10.1074/jbc.M114.605980. Epub 2014 Dec 4.

引用本文的文献

1
A critical role for in negatively impacting metformin response in diabetes.在对糖尿病患者二甲双胍反应产生负面影响中起关键作用。 （注：原文中“in”前面缺少具体内容，翻译可能不太准确，需结合完整原文进一步完善。）
Acta Pharm Sin B. 2025 May;15(5):2511-2528. doi: 10.1016/j.apsb.2025.02.008. Epub 2025 Feb 11.
2
Effects of rhamnolipids on growth performance, gut barriers, antioxidant capacity, immune function, and gut microbiota in broiler chickens.鼠李糖脂对肉鸡生长性能、肠道屏障、抗氧化能力、免疫功能和肠道微生物群的影响。
Poult Sci. 2025 May;104(5):104919. doi: 10.1016/j.psj.2025.104919. Epub 2025 Feb 17.
3
MMP12-dependent myofibroblast formation contributes to nucleus pulposus fibrosis.

本文引用的文献

1
Omics era in type 2 diabetes: From childhood to adulthood.2型糖尿病的组学时代：从儿童期到成年期。
World J Diabetes. 2021 Dec 15;12(12):2027-2035. doi: 10.4239/wjd.v12.i12.2027.
2
The trend in application of omics in type 2 diabetes researches; A bibliometric study.二代糖尿病研究中组学应用趋势：文献计量研究。
Diabetes Metab Syndr. 2021 Sep-Oct;15(5):102250. doi: 10.1016/j.dsx.2021.102250. Epub 2021 Aug 17.
3
The role of adipose tissue M1/M2 macrophages in type 2 diabetes mellitus.脂肪组织M1/M2巨噬细胞在2型糖尿病中的作用。
基质金属蛋白酶12依赖性肌成纤维细胞的形成导致髓核纤维化。
JCI Insight. 2025 Mar 4;10(7):e180809. doi: 10.1172/jci.insight.180809.
4
Host response to cholestyramine can be mediated by the gut microbiota.宿主对消胆胺的反应可能由肠道微生物群介导。
Microbiome Res Rep. 2024 Jul 11;3(4):40. doi: 10.20517/mrr.2023.82. eCollection 2024.
5
Exploring the design of clinical research studies on the efficacy mechanisms in type 2 diabetes mellitus.探讨 2 型糖尿病疗效机制的临床研究设计。
Front Endocrinol (Lausanne). 2024 Sep 20;15:1363877. doi: 10.3389/fendo.2024.1363877. eCollection 2024.
6
Specific Gut Microbiome Signatures in Children with Cow's Milk Allergy.牛奶过敏儿童的特定肠道微生物组特征。
Nutrients. 2024 Aug 18;16(16):2752. doi: 10.3390/nu16162752.
7
Intestinal Nogo-B reduces GLP1 levels by binding to proglucagon on the endoplasmic reticulum to inhibit PCSK1 cleavage.肠内 Nogo-B 通过与内质网上的胰高血糖素原结合来减少 GLP1 水平，从而抑制 PCSK1 的切割。
Nat Commun. 2024 Aug 10;15(1):6845. doi: 10.1038/s41467-024-51352-3.
8
Exploration of the shared pathways and common biomarker in adamantinomatous craniopharyngioma and type 2 diabetes using integrated bioinformatics analysis.基于整合生物信息学分析的颅咽管瘤和 2 型糖尿病相关通路和共同生物标志物的研究。
PLoS One. 2024 Jun 7;19(6):e0304404. doi: 10.1371/journal.pone.0304404. eCollection 2024.
9
Flavonoids, gut microbiota, and host lipid metabolism.类黄酮、肠道微生物群与宿主脂质代谢。
Eng Life Sci. 2023 Nov 13;24(5):2300065. doi: 10.1002/elsc.202300065. eCollection 2024 May.
10
Implications of the Matrix Metalloproteinases, Their Tissue Inhibitors and Some Other Inflammatory Mediators Expression Levels in Children Obesity-Related Phenotypes.基质金属蛋白酶及其组织抑制剂以及其他一些炎症介质的表达水平在儿童肥胖相关表型中的意义
J Pers Med. 2024 Mar 19;14(3):317. doi: 10.3390/jpm14030317.
Diabetol Int. 2020 Dec 15;12(1):74-79. doi: 10.1007/s13340-020-00482-2. eCollection 2021 Jan.
4
Transkingdom interactions between Lactobacilli and hepatic mitochondria attenuate western diet-induced diabetes.厚壁菌门细菌与肝线粒体之间的跨界相互作用可减轻西式饮食诱导的糖尿病。
Nat Commun. 2021 Jan 4;12(1):101. doi: 10.1038/s41467-020-20313-x.
5
The Gut Microbiome and Individual-Specific Responses to Diet.肠道微生物群与个体对饮食的特异性反应。
mSystems. 2020 Sep 29;5(5):e00665-20. doi: 10.1128/mSystems.00665-20.
6
Mitochondria and T2D: Role of Autophagy, ER Stress, and Inflammasome.线粒体与 T2D：自噬、内质网应激和炎症小体的作用。
Trends Endocrinol Metab. 2020 Oct;31(10):725-741. doi: 10.1016/j.tem.2020.03.004. Epub 2020 Apr 4.
7
Application of information theory in systems biology.信息论在系统生物学中的应用。
Biophys Rev. 2020 Apr;12(2):377-384. doi: 10.1007/s12551-020-00665-w. Epub 2020 Mar 6.
8
Single-cell analysis of human adipose tissue identifies depot and disease specific cell types.对人体脂肪组织的单细胞分析确定了脂肪组织和疾病特异性细胞类型。
Nat Metab. 2020 Jan;2(1):97-109. doi: 10.1038/s42255-019-0152-6. Epub 2019 Dec 23.
9
Role of gut microbiota in type 2 diabetes pathophysiology.肠道微生物群在 2 型糖尿病发病机制中的作用。
EBioMedicine. 2020 Jan;51:102590. doi: 10.1016/j.ebiom.2019.11.051. Epub 2020 Jan 3.
10
Whole Transcriptome Analysis of Obese Adipose Tissue Suggests u001kfc.1 as a Potential Regulator to Glucose Homeostasis.肥胖脂肪组织的全转录组分析表明u001kfc.1是葡萄糖稳态的潜在调节因子。
Front Genet. 2019 Nov 21;10:1133. doi: 10.3389/fgene.2019.01133. eCollection 2019.