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Lipid-Associated Macrophages Control Metabolic Homeostasis in a Trem2-Dependent Manner
- 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.
- Subjects :
- Systems biology
Adipose Tissue, White
Cell
Adipose tissue
White adipose tissue
Biology
Intra-Abdominal Fat
Diet, High-Fat
General Biochemistry, Genetics and Molecular Biology
Monocytes
Article
Pathogenesis
03 medical and health sciences
Mice
0302 clinical medicine
Immune system
Glucose Intolerance
medicine
Macrophage
Animals
Humans
Obesity
Receptors, Immunologic
030304 developmental biology
Mice, Knockout
0303 health sciences
Membrane Glycoproteins
Macrophages
Lipid Metabolism
Lipids
Cell biology
Mice, Inbred C57BL
medicine.anatomical_structure
Adipocyte hypertrophy
Single-Cell Analysis
030217 neurology & neurosurgery
Signal Transduction
Subjects
Details
- ISSN :
- 10974172
- Volume :
- 178
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Cell
- Accession number :
- edsair.doi.dedup.....565a0585c21c157caa2807dc71bbc37c