TY - JOUR
T1 - Lipid-Associated Macrophages Control Metabolic Homeostasis in a Trem2-Dependent Manner
AU - Jaitin, Diego Adhemar
AU - Adlung, Lorenz
AU - Thaiss, Christoph A.
AU - Weiner, Assaf
AU - Li, Baoguo
AU - Descamps, Hélène
AU - Lundgren, Patrick
AU - Bleriot, Camille
AU - Liu, Zhaoyuan
AU - Deczkowska, Aleksandra
AU - Keren-Shaul, Hadas
AU - David, Eyal
AU - Zmora, Niv
AU - Eldar, Shai Meron
AU - Lubezky, Nir
AU - Shibolet, Oren
AU - Hill, David A.
AU - Lazar, Mitchell A.
AU - Colonna, Marco
AU - Ginhoux, Florent
AU - Shapiro, Hagit
AU - Elinav, Eran
AU - Amit, Ido
N1 - Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/7/25
Y1 - 2019/7/25
N2 - 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.
AB - 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.
KW - Alzheimer disease
KW - Trem2 pathway
KW - fatty liver diseases
KW - immunology
KW - macrophages
KW - metabolic diseases
KW - metabolism
KW - obesity
KW - single-cell genomics
KW - systems biology
UR - http://www.scopus.com/inward/record.url?scp=85069726280&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2019.05.054
DO - 10.1016/j.cell.2019.05.054
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C2 - 31257031
AN - SCOPUS:85069726280
SN - 0092-8674
VL - 178
SP - 686-698.e14
JO - Cell
JF - Cell
IS - 3
ER -