{"title":"单细胞景观和巨噬细胞亚群增强糖尿病棕色脂肪细胞的功能","authors":"Junfei Gu, Jiajia Jin, Xiaoyu Ren, Xinjie Zhang, Jiaxuan Li, Xiaowei Wang, Shucui Zhang, Xianlun Yin, Qunye Zhang, Zhe Wang","doi":"10.4093/dmj.2023.0278","DOIUrl":null,"url":null,"abstract":"<p><strong>Backgruound: </strong>Metabolic dysregulation is a hallmark of type 2 diabetes mellitus (T2DM), in which the abnormalities in brown adipose tissue (BAT) play important roles. However, the cellular composition and function of BAT as well as its pathological significance in diabetes remain incompletely understood. Our objective is to delineate the single-cell landscape of BAT-derived stromal vascular fraction (SVF) and their characteristic alterations in T2DM rats.</p><p><strong>Methods: </strong>T2DM was induced in rats by intraperitoneal injection of low-dose streptozotocin and high-fat diet feeding. Single-cell mRNA sequencing was then performed on BAT samples and compared to normal rats to characterize changes in T2DM rats. Subsequently, the importance of key cell subsets in T2DM was elucidated using various functional studies.</p><p><strong>Results: </strong>Almost all cell types in the BAT-derived SVF of T2DM rats exhibited enhanced inflammatory responses, increased angiogenesis, and disordered glucose and lipid metabolism. The multidirectional differentiation potential of adipose tissue-derived stem cells was also reduced. Moreover, macrophages played a pivotal role in intercellular crosstalk of BAT-derived SVF. A novel Rarres2+macrophage subset promoted the differentiation and metabolic function of brown adipocytes via adipose-immune crosstalk.</p><p><strong>Conclusion: </strong>BAT SVF exhibited strong heterogeneity in cellular composition and function and contributed to T2DM as a significant inflammation source, in which a novel macrophage subset was identified that can promote brown adipocyte function.</p>","PeriodicalId":11153,"journal":{"name":"Diabetes & Metabolism Journal","volume":null,"pages":null},"PeriodicalIF":6.8000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11449828/pdf/","citationCount":"0","resultStr":"{\"title\":\"Single-Cell Landscape and a Macrophage Subset Enhancing Brown Adipocyte Function in Diabetes.\",\"authors\":\"Junfei Gu, Jiajia Jin, Xiaoyu Ren, Xinjie Zhang, Jiaxuan Li, Xiaowei Wang, Shucui Zhang, Xianlun Yin, Qunye Zhang, Zhe Wang\",\"doi\":\"10.4093/dmj.2023.0278\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Backgruound: </strong>Metabolic dysregulation is a hallmark of type 2 diabetes mellitus (T2DM), in which the abnormalities in brown adipose tissue (BAT) play important roles. However, the cellular composition and function of BAT as well as its pathological significance in diabetes remain incompletely understood. Our objective is to delineate the single-cell landscape of BAT-derived stromal vascular fraction (SVF) and their characteristic alterations in T2DM rats.</p><p><strong>Methods: </strong>T2DM was induced in rats by intraperitoneal injection of low-dose streptozotocin and high-fat diet feeding. Single-cell mRNA sequencing was then performed on BAT samples and compared to normal rats to characterize changes in T2DM rats. Subsequently, the importance of key cell subsets in T2DM was elucidated using various functional studies.</p><p><strong>Results: </strong>Almost all cell types in the BAT-derived SVF of T2DM rats exhibited enhanced inflammatory responses, increased angiogenesis, and disordered glucose and lipid metabolism. The multidirectional differentiation potential of adipose tissue-derived stem cells was also reduced. 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A novel Rarres2+macrophage subset promoted the differentiation and metabolic function of brown adipocytes via adipose-immune crosstalk.</p><p><strong>Conclusion: </strong>BAT SVF exhibited strong heterogeneity in cellular composition and function and contributed to T2DM as a significant inflammation source, in which a novel macrophage subset was identified that can promote brown adipocyte function.</p>\",\"PeriodicalId\":11153,\"journal\":{\"name\":\"Diabetes & Metabolism Journal\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.8000,\"publicationDate\":\"2024-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11449828/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Diabetes & Metabolism Journal\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.4093/dmj.2023.0278\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/5/29 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetes & Metabolism Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.4093/dmj.2023.0278","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/5/29 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0
摘要
背景：代谢失调是 2 型糖尿病（T2DM）的特征之一，棕色脂肪组织（BAT）的异常在其中发挥着重要作用。然而，人们对棕色脂肪组织的细胞组成和功能及其在糖尿病中的病理意义仍不甚了解。我们的目的是描述棕色脂肪组织衍生的基质血管组分（SVF）的单细胞结构及其在 T2DM 大鼠中的特征性改变：方法：通过腹腔注射低剂量链脲佐菌素和喂食高脂饮食诱导大鼠患上 T2DM。然后对 BAT 样本进行单细胞 mRNA 测序，并与正常大鼠进行比较，以确定 T2DM 大鼠的变化特征。随后，通过各种功能研究阐明了关键细胞亚群在 T2DM 中的重要性：结果：T2DM 大鼠 BAT 衍生 SVF 中的几乎所有细胞类型都表现出炎症反应增强、血管生成增加以及葡萄糖和脂质代谢紊乱。脂肪组织衍生干细胞的多向分化潜能也降低了。此外，巨噬细胞在 BAT 衍生 SVF 的细胞间串联中发挥了关键作用。一个新的Rarres2+巨噬细胞亚群通过脂肪-免疫串联促进了棕色脂肪细胞的分化和代谢功能：BAT SVF在细胞组成和功能方面表现出很强的异质性，是导致T2DM的一个重要炎症来源，其中一个新型巨噬细胞亚群可促进棕色脂肪细胞的功能。
Single-Cell Landscape and a Macrophage Subset Enhancing Brown Adipocyte Function in Diabetes.
Backgruound: Metabolic dysregulation is a hallmark of type 2 diabetes mellitus (T2DM), in which the abnormalities in brown adipose tissue (BAT) play important roles. However, the cellular composition and function of BAT as well as its pathological significance in diabetes remain incompletely understood. Our objective is to delineate the single-cell landscape of BAT-derived stromal vascular fraction (SVF) and their characteristic alterations in T2DM rats.
Methods: T2DM was induced in rats by intraperitoneal injection of low-dose streptozotocin and high-fat diet feeding. Single-cell mRNA sequencing was then performed on BAT samples and compared to normal rats to characterize changes in T2DM rats. Subsequently, the importance of key cell subsets in T2DM was elucidated using various functional studies.
Results: Almost all cell types in the BAT-derived SVF of T2DM rats exhibited enhanced inflammatory responses, increased angiogenesis, and disordered glucose and lipid metabolism. The multidirectional differentiation potential of adipose tissue-derived stem cells was also reduced. Moreover, macrophages played a pivotal role in intercellular crosstalk of BAT-derived SVF. A novel Rarres2+macrophage subset promoted the differentiation and metabolic function of brown adipocytes via adipose-immune crosstalk.
Conclusion: BAT SVF exhibited strong heterogeneity in cellular composition and function and contributed to T2DM as a significant inflammation source, in which a novel macrophage subset was identified that can promote brown adipocyte function.
期刊介绍：
The aims of the Diabetes & Metabolism Journal are to contribute to the cure of and education about diabetes mellitus, and the advancement of diabetology through the sharing of scientific information on the latest developments in diabetology among members of the Korean Diabetes Association and other international societies.
The Journal publishes articles on basic and clinical studies, focusing on areas such as metabolism, epidemiology, pathogenesis, complications, and treatments relevant to diabetes mellitus. It also publishes articles covering obesity and cardiovascular disease. Articles on translational research and timely issues including ubiquitous care or new technology in the management of diabetes and metabolic disorders are welcome. In addition, genome research, meta-analysis, and randomized controlled studies are welcome for publication.
The editorial board invites articles from international research or clinical study groups. Publication is determined by the editors and peer reviewers, who are experts in their specific fields of diabetology.
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