Control of lipolysis by a population of oxytocinergic sympathetic neurons

Oxytocin (OXT), a nine amino acid peptide produced in the hypothalamus and released by the posterior pituitary, has well-known actions in parturition, lactation, and social behavior 1 , and has become an intriguing therapeutic target for diseases like autism and schizophrenia 2 . Exogenous OXT has also been shown to promote weight loss, among other beneficial metabolic effects 1,3 , suggesting that its therapeutic potential may extend to diabetes and obesity 1,4 . It is unclear, however, whether endogenous OXT participates in metabolic homeostasis. Here we show that OXT is a critical regulator of adipose tissue lipolysis in both mice and humans. In addition, OXT serves to license the ability of β- adrenergic agonists to fully promote lipolysis. Most surprisingly, the relevant source of OXT in these metabolic actions is a previously unidentified subpopulation of tyrosine hydroxylase (TH)-positive sympathetic neurons. Our data reveal that OXT from the peripheral nervous system is an endogenous regulator of adipose and systemic metabolism.