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 β₂ 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.

中文翻译：

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皮下脂肪中乙酰胆碱合成巨噬细胞受 β2-肾上腺素能信号调节


由乙酰胆碱介导的非神经元胆碱能信号在炎症和免疫等生理过程中发挥重要作用。我们的小组首先发现了脂肪组织中非神经元胆碱能回路的证据，免疫细胞在适应性产热过程中分泌乙酰胆碱来激活米色脂肪细胞。在这里，我们揭示巨噬细胞是负责分泌乙酰胆碱以调节皮下脂肪生热激活的细胞主角，我们将这些细胞称为胆​​碱能脂肪巨噬细胞（ChAM）。急性寒冷暴露后，ChAM 丰度明显适应性增加，巨噬细胞特异性删除胆碱乙酰转移酶 (ChAT)（乙酰胆碱生物合成酶），损害小鼠寒冷诱导的生热能力。此外，利用药理学和遗传学方法，我们发现 ChAM 通过肾上腺素信号传导，特别是通过 β ₂肾上腺素受体进行调节。这些发现表明，巨噬细胞是调节适应性产热的乙酰胆碱的重要脂肪组织来源，并且可能有助于代谢疾病的治疗靶向。