Resident macrophages restrain pathological adipose tissue remodeling and protect vascular integrity in obese mice

Qi Chen; Si Min Lai; Shaohai Xu; Yingrou Tan; Keith Leong; Dehua Liu; Jia Chi Tan; Roshan Ratnakar Naik; Anna M. Barron; Sunil S. Adav; Jinmiao Chen; Shu Zhen Chong; Lai Guan Ng; Christiane Ruedl

doi:10.15252/embr.202152835

Resident macrophages restrain pathological adipose tissue remodeling and protect vascular integrity in obese mice

Qi Chen, Si Min Lai, Shaohai Xu, Yingrou Tan, Keith Leong, Dehua Liu, Jia Chi Tan, Roshan Ratnakar Naik, Anna M. Barron, Sunil S. Adav, Jinmiao Chen, Shu Zhen Chong, Lai Guan Ng, Christiane Ruedl^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

32 Citations (Scopus)

Abstract

Tissue-resident macrophages in white adipose tissue (WAT) dynamically adapt to the metabolic changes of their microenvironment that are often induced by excess energy intake. Currently, the exact contribution of these macrophages in obesity-driven WAT remodeling remains controversial. Here, using a transgenic CD169-DTR mouse strain, we provide new insights into the interplay between CD169⁺ adipose tissue macrophages (ATMs) and their surrounding WAT microenvironment. Using targeted in vivo ATM ablation followed by transcriptional and metabolic WAT profiling, we found that ATMs protect WAT from the excessive pathological remodeling that occurs during obesity. As obesity progresses, ATMs control not only vascular integrity, adipocyte function, and lipid and metabolic derangements but also extracellular matrix accumulation and resultant fibrosis in the WAT. The protective role of ATMs during obesity-driven WAT dysfunction supports the notion that ATMs represent friends, rather than foes, as has previously assumed.

Original language	English
Article number	e52835
Journal	EMBO Reports
Volume	22
Issue number	8
DOIs	https://doi.org/10.15252/embr.202152835
Publication status	Published - Aug 4 2021
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2021 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

ASJC Scopus Subject Areas

Biochemistry
Molecular Biology
Genetics

Keywords

adipocyte hypertrophy
fibrosis
obesity-mediated adipose tissue remodeling
tissue-resident macrophages
vascular integrity

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.15252/embr.202152835

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title = "Resident macrophages restrain pathological adipose tissue remodeling and protect vascular integrity in obese mice",

abstract = "Tissue-resident macrophages in white adipose tissue (WAT) dynamically adapt to the metabolic changes of their microenvironment that are often induced by excess energy intake. Currently, the exact contribution of these macrophages in obesity-driven WAT remodeling remains controversial. Here, using a transgenic CD169-DTR mouse strain, we provide new insights into the interplay between CD169+ adipose tissue macrophages (ATMs) and their surrounding WAT microenvironment. Using targeted in vivo ATM ablation followed by transcriptional and metabolic WAT profiling, we found that ATMs protect WAT from the excessive pathological remodeling that occurs during obesity. As obesity progresses, ATMs control not only vascular integrity, adipocyte function, and lipid and metabolic derangements but also extracellular matrix accumulation and resultant fibrosis in the WAT. The protective role of ATMs during obesity-driven WAT dysfunction supports the notion that ATMs represent friends, rather than foes, as has previously assumed.",

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doi = "10.15252/embr.202152835",

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AU - Chen, Qi

AU - Lai, Si Min

AU - Xu, Shaohai

AU - Tan, Yingrou

AU - Leong, Keith

AU - Liu, Dehua

AU - Tan, Jia Chi

AU - Naik, Roshan Ratnakar

AU - Barron, Anna M.

AU - Adav, Sunil S.

AU - Chen, Jinmiao

AU - Chong, Shu Zhen

AU - Ng, Lai Guan

AU - Ruedl, Christiane

PY - 2021/8/4

Y1 - 2021/8/4

N2 - Tissue-resident macrophages in white adipose tissue (WAT) dynamically adapt to the metabolic changes of their microenvironment that are often induced by excess energy intake. Currently, the exact contribution of these macrophages in obesity-driven WAT remodeling remains controversial. Here, using a transgenic CD169-DTR mouse strain, we provide new insights into the interplay between CD169+ adipose tissue macrophages (ATMs) and their surrounding WAT microenvironment. Using targeted in vivo ATM ablation followed by transcriptional and metabolic WAT profiling, we found that ATMs protect WAT from the excessive pathological remodeling that occurs during obesity. As obesity progresses, ATMs control not only vascular integrity, adipocyte function, and lipid and metabolic derangements but also extracellular matrix accumulation and resultant fibrosis in the WAT. The protective role of ATMs during obesity-driven WAT dysfunction supports the notion that ATMs represent friends, rather than foes, as has previously assumed.

AB - Tissue-resident macrophages in white adipose tissue (WAT) dynamically adapt to the metabolic changes of their microenvironment that are often induced by excess energy intake. Currently, the exact contribution of these macrophages in obesity-driven WAT remodeling remains controversial. Here, using a transgenic CD169-DTR mouse strain, we provide new insights into the interplay between CD169+ adipose tissue macrophages (ATMs) and their surrounding WAT microenvironment. Using targeted in vivo ATM ablation followed by transcriptional and metabolic WAT profiling, we found that ATMs protect WAT from the excessive pathological remodeling that occurs during obesity. As obesity progresses, ATMs control not only vascular integrity, adipocyte function, and lipid and metabolic derangements but also extracellular matrix accumulation and resultant fibrosis in the WAT. The protective role of ATMs during obesity-driven WAT dysfunction supports the notion that ATMs represent friends, rather than foes, as has previously assumed.

KW - adipocyte hypertrophy

KW - fibrosis

KW - obesity-mediated adipose tissue remodeling

KW - tissue-resident macrophages

KW - vascular integrity

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Resident macrophages restrain pathological adipose tissue remodeling and protect vascular integrity in obese mice

Abstract

Bibliographical note

ASJC Scopus Subject Areas

Keywords

UN SDGs

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