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单细胞景观及促进糖尿病棕色脂肪细胞功能的巨噬细胞亚群

Single-Cell Landscape and a Macrophage Subset Enhancing Brown Adipocyte Function in Diabetes.

机构信息

Department of Endocrinology & Geriatrics, Shandong Provincial Hospital, Shandong University, Jinan, China.

Department of Geriatrics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.

出版信息

Diabetes Metab J. 2024 Sep;48(5):885-900. doi: 10.4093/dmj.2023.0278. Epub 2024 May 29.

DOI:10.4093/dmj.2023.0278
PMID:38853519
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11449828/
Abstract

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.

摘要

背景

代谢失调是 2 型糖尿病（T2DM）的一个标志，其中棕色脂肪组织（BAT）的异常起着重要作用。然而，BAT 的细胞组成和功能及其在糖尿病中的病理意义仍不完全清楚。我们的目的是描绘 BAT 衍生的基质血管部分（SVF）的单细胞景观及其在 T2DM 大鼠中的特征改变。

方法

通过腹腔注射小剂量链脲佐菌素和高脂饮食喂养诱导大鼠 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，以表征 T2DM 大鼠的变化。随后，使用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 衍生的 SVF 中的几乎所有细胞类型都表现出增强的炎症反应、增加的血管生成以及葡萄糖和脂质代谢紊乱。脂肪组织来源干细胞的多向分化潜能也降低了。此外，巨噬细胞在 BAT 衍生的 SVF 细胞间通讯中起着关键作用。一种新型的 Rarres2+巨噬细胞亚群通过脂肪免疫相互作用促进棕色脂肪细胞的分化和代谢功能。

结论

BAT SVF 在细胞组成和功能上表现出很强的异质性，并作为一个重要的炎症源促进了 T2DM 的发生，其中鉴定出一种新型的巨噬细胞亚群，它可以促进棕色脂肪细胞的功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdba/11449828/1d102980a67c/dmj-2023-0278f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdba/11449828/48df52a6589a/dmj-2023-0278f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdba/11449828/5cf51aa71edb/dmj-2023-0278f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdba/11449828/780bc6fe5cd7/dmj-2023-0278f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdba/11449828/3e31a8fb0e7e/dmj-2023-0278f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdba/11449828/ad8da0c21d60/dmj-2023-0278f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdba/11449828/a39281c78588/dmj-2023-0278f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdba/11449828/1d102980a67c/dmj-2023-0278f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdba/11449828/48df52a6589a/dmj-2023-0278f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdba/11449828/5cf51aa71edb/dmj-2023-0278f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdba/11449828/780bc6fe5cd7/dmj-2023-0278f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdba/11449828/3e31a8fb0e7e/dmj-2023-0278f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdba/11449828/ad8da0c21d60/dmj-2023-0278f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdba/11449828/a39281c78588/dmj-2023-0278f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdba/11449828/1d102980a67c/dmj-2023-0278f7.jpg

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