Control of lipolysis by a population of oxytocinergic sympathetic neurons

• 成果类型: Article
• 署名作者: Li, Erwei; Wang, Luhong; Wang, Daqing; Chi, Jingyi; Lin, Zeran; Smith, Gordon I.; Klein, Samuel; Cohen, Paul; Rosen, Evan D.
• 署名单位: Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard University; Harvard Medical School; Rockefeller University; Washington University (WUSTL); Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute
• 刊物名称: Nature
• ISSN/ISSBN: 0028-4771
• DOI: 10.1038/s41586-023-06830-x
• 发表日期: 2024-01-04
• 关键词: hormone-sensitive lipase; adipocyte lipolysis; glucose-metabolism; perilipin; mouse; PATHWAY; tissues

摘要

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 behaviour1, and has become an intriguing therapeutic target for conditions such as autism and schizophrenia2. Exogenous OXT has also been shown to have effects on body weight, lipid levels and glucose homeostasis1,3, suggesting that it may also have therapeutic potential for metabolic disease1,4. 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 facilitate the ability of beta-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-positive sympathetic neurons. Our data reveal that OXT from the peripheral nervous system is an endogenous regulator of adipose and systemic metabolism. Oxytocin derived from peripheral sympathetic neurons is shown to regulate lipolysis and systemic metabolism.