Sensory-neuron-derived CGRPα controls white adipocyte differentiation and tissue plasticity

Communication between the brain and adipose tissue is mediated in part by the peripheral nervous system. The sympathetic branch transmits lipolytic and thermogenic signals toward adipose tissue, while sensory nerves relay information to the central nervous system. Importantly, sensory nerve activation also triggers local neuropeptide release. Here, we show that sensory-neuron-derived α-calcitonin gene-related peptide (CGRPα) inhibits white, but not brown, preadipocyte differentiation in a cell-autonomous manner. In vivo, CGRPα expression in mouse subcutaneous adipose tissue during cold exposure shifts the expected increase in smaller adipocytes to an increase in larger cells. Importantly, people on anti-CGRPα/CGRP receptor (CGRPR) medications for migraine treatment show reductions in weight and glycemia, while these measures increase in the matched control group. Similarly, mice treated with a CGRPR antagonist and exposed to cold show a reduction in body weight. These findings identify a neuron-adipocyte communication pathway that regulates white adipose tissue plasticity and metabolism.