CHRNA2: a new paradigm in beige thermoregulation and metabolism

The contribution of thermogenic adipocytes to maintain systemic metabolic homeostasis has been increasingly appreciated in recent years. It is now recognized that different types (e.g., brown, beige) and subtypes of thermogenic adipocytes may arise from various developmental origins. In addition to the adrenergic pathway, other signals can activate thermogenesis, including paracrine communication between immune cells within the adipose tissue niche and thermogenic adipocytes. In this opinion article we highlight the recently discovered beige-selective signaling between acetylcholine from immune cells and cholinergic receptor nicotinic alpha 2 subunit (CHRNA2) in activated beige adipocytes. We present our current knowledge of how this previously unrecognized adipose non-neuronal cholinergic signaling pathway mediates beige thermoregulation, and discuss its impact on whole-body fitness and its therapeutic potential as a novel target for combating metabolic disease.