Acetylcholine‐synthesizing macrophages in subcutaneous fat are regulated by β 2 ‐adrenergic signaling
| Autor: | Victoria S Nudell, Matthew J. Sorensen, Heejin Jun, Yingxu Ma, Robert T. Kennedy, Li Ye, Shanshan Liu, Alexander J. Knights, Ivan Maillard, Eric Perkey, Jun Wu |
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| Rok vydání: | 2021 |
| Předmět: |
Primary Cell Culture
Subcutaneous Fat Adipose tissue Inflammation Biology General Biochemistry Genetics and Molecular Biology Choline O-Acetyltransferase Gene Knockout Techniques Mice Immune system medicine Animals Secretion Molecular Biology Cells Cultured General Immunology and Microbiology Macrophages General Neuroscience Thermogenesis Articles Choline acetyltransferase Acetylcholine Cell biology Cold Temperature Cholinergic Receptors Adrenergic beta-2 medicine.symptom Gene Deletion medicine.drug |
| Zdroj: | EMBO J |
| ISSN: | 1460-2075 0261-4189 |
| DOI: | 10.15252/embj.2020106061 |
| Popis: | Non‐neuronal cholinergic signaling, mediated by acetylcholine, plays important roles in physiological processes including inflammation and immunity. Our group first discovered evidence of non‐neuronal cholinergic circuitry in adipose tissue, whereby immune cells secrete acetylcholine to activate beige adipocytes during adaptive thermogenesis. Here, we reveal that macrophages are the cellular protagonists responsible for secreting acetylcholine to regulate thermogenic activation in subcutaneous fat, and we term these cells cholinergic adipose macrophages (ChAMs). An adaptive increase in ChAM abundance is evident following acute cold exposure, and macrophage‐specific deletion of choline acetyltransferase (ChAT), the enzyme for acetylcholine biosynthesis, impairs the cold‐induced thermogenic capacity of mice. Further, using pharmacological and genetic approaches, we show that ChAMs are regulated via adrenergic signaling, specifically through the β(2) adrenergic receptor. These findings demonstrate that macrophages are an essential adipose tissue source of acetylcholine for the regulation of adaptive thermogenesis, and may be useful for therapeutic targeting in metabolic diseases. |
| Databáze: | OpenAIRE |
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