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Lipid-Associated Macrophages Control Metabolic Homeostasis in a Trem2-Dependent Manner

Authors :
Assaf Weiner
Zhaoyuan Liu
Aleksandra Deczkowska
Hagit Shapiro
Nir Lubezky
Patrick Lundgren
Baoguo Li
Ido Amit
Diego Jaitin
Hadas Keren-Shaul
Lorenz Adlung
Eyal David
Eran Elinav
Mitchell A. Lazar
Marco Colonna
Shai Meron Eldar
Hélène Descamps
Camille Blériot
Oren Shibolet
David A. Hill
Christoph A. Thaiss
Niv Zmora
Florent Ginhoux
Source :
Cell
Publication Year :
2019

Abstract

Immune cells residing in white adipose tissue have been highlighted as important factors contributing to the pathogenesis of metabolic diseases, but the molecular regulators that drive adipose tissue immune cell remodeling during obesity remain largely unknown. Using index and transcriptional single-cell sorting, we comprehensively map all adipose tissue immune populations in both mice and humans during obesity. We describe a novel and conserved Trem2(+) lipid-associated macrophage (LAM) subset and identify markers, spatial localization, origin, and functional pathways associated with these cells. Genetic ablation of Trem2 in mice globally inhibits the downstream molecular LAM program, leading to adipocyte hypertrophy as well as systemic hypercholesterolemia, body fat accumulation, and glucose intolerance. These findings identify Trem2 signaling as a major pathway by which macrophages respond to loss of tissue-level lipid homeostasis, highlighting Trem2 as a key sensor of metabolic pathologies across multiple tissues and a potential therapeutic target in metabolic diseases.

Details

ISSN :
10974172
Volume :
178
Issue :
3
Database :
OpenAIRE
Journal :
Cell
Accession number :
edsair.doi.dedup.....565a0585c21c157caa2807dc71bbc37c