Immune cell cholinergic signaling in adipose thermoregulation and immunometabolism

Research focusing on adipose immunometabolism has been expanded from inflammation in white fat during obesity development to immune cell function regulating thermogenic fat, energy expenditure, and systemic metabolism. This opinion discusses our current understanding of how resident immune cells within the thermogenic fat niche may regulate whole-body energy homeostasis. Furthermore, various types of immune cells can synthesize acetylcholine (ACh) and regulate important physiological functions. We highlight a unique subset of cholinergic macrophages within subcutaneous adipose tissue, termed cholinergic adipose macrophages (ChAMs); these macrophages interact with beige adipocytes through cholinergic receptor nicotinic alpha 2 subunit (CHRNA2) signaling to induce adaptive thermogenesis. We posit that these newly identified thermoregulatory macrophages may broaden our view of immune system functions for maintaining metabolic homeostasis and potentially treating obesity and metabolic disorders.