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Macrophage beta2-adrenergic receptor is dispensable for the adipose tissue inflammation and function
- Source :
- Molecular Metabolism, Vol 48, Iss, Pp 101220-(2021), Molecular Metabolism
- Publication Year :
- 2021
- Publisher :
- Elsevier, 2021.
-
Abstract
- Objective Neuroimmune interactions between the sympathetic nervous system (SNS) and macrophages are required for the homeostasis of multiple tissues, including the adipose tissue. It has been proposed that the SNS maintains adipose tissue macrophages (ATMs) in an anti-inflammatory state via direct norepinephrine (NE) signaling to macrophages. This study aimed to investigate the physiological importance of this paradigm by utilizing a mouse model in which the adrenergic signaling from the SNS to macrophages, but not to other adipose tissue cells, was disrupted. Methods We generated a macrophage-specific B2AR knockout mouse (Adrb2ΔLyz2) by crossing Adrb2fl/fl and Lyz2Cre/+ mice. We have previously shown that macrophages isolated from Adrb2ΔLyz2 animals do not respond to NE stimulation in vitro. Herein we performed a metabolic phenotyping of Adrb2ΔLyz2 mice on either chow or high-fat diet (HFD). We also assessed the adipose tissue function of Adrb2ΔLyz2 animals during fasting and cold exposure. Finally, we transplanted Adrb2ΔLyz2 bone marrow to low-density lipoprotein receptor (LDLR) knockout mice and investigated the development of atherosclerosis during Western diet feeding. Results We demonstrated that SNS-associated ATMs have a transcriptional profile indicative of activated beta-2 adrenergic receptor (B2AR), the main adrenergic receptor isoform in myeloid cells. However, Adrb2ΔLyz2 mice have unaltered energy balance on a chow or HFD. Furthermore, Adrb2ΔLyz2 mice show similar levels of adipose tissue inflammation and function during feeding, fasting, or cold exposure, and develop insulin resistance during HFD at the same rate as controls. Finally, macrophage-specific B2AR deletion does not affect the development of atherosclerosis on an LDL receptor-null genetic background. Conclusions Overall, our data suggest that the SNS does not directly modulate the phenotype of adipose tissue macrophages in either lean mice or mouse models of cardiometabolic disease. Instead, sympathetic nerve activity exerts an indirect effect on adipose tissue macrophages through the modulation of adipocyte function.<br />Graphical abstract Image 1<br />Highlights • Sympathetic nerve-associated macrophages in white adipose tissues exhibit a transcriptional signature of B2AR activation. • Macrophage-specific B2AR knockout does not affect the phenotype of adipose tissue macrophages. • Macrophage B2AR signaling does not affect adipose tissue function during fasting or cold exposure. • Macrophage B2AR is dispensable for the development of insulin resistance and atherosclerosis in obesity.
- Subjects :
- 0301 basic medicine
Male
Panniculitis
Sympathetic Nervous System
Adipose tissue
chemistry.chemical_compound
Mice
Norepinephrine
0302 clinical medicine
Adipocyte
Adipocytes
Receptor
Internal medicine
Cells, Cultured
Bone Marrow Transplantation
Mice, Knockout
Phenotype
Knockout mouse
Original Article
Female
medicine.symptom
Sympathetic
Signal Transduction
medicine.medical_specialty
Adrenergic receptor
Adipose tissue macrophages
Adipose Tissue, White
030209 endocrinology & metabolism
Inflammation
Biology
Neuroimmune
Diet, High-Fat
03 medical and health sciences
medicine
Animals
Obesity
Molecular Biology
Immunometabolism
adrb2
Macrophages
Cell Biology
Atherosclerosis
RC31-1245
Mice, Inbred C57BL
Disease Models, Animal
030104 developmental biology
Endocrinology
chemistry
Diet, Western
LDL receptor
Receptors, Adrenergic, beta-2
Insulin Resistance
Subjects
Details
- Language :
- English
- ISSN :
- 22128778
- Volume :
- 48
- Database :
- OpenAIRE
- Journal :
- Molecular Metabolism
- Accession number :
- edsair.doi.dedup.....e9687b67a96b5777b397572888d953e8