Oxytocin regulates body composition

Li Sun, Daria Lizneva, Yaoting Ji, Graziana Colaianni, Elina Hadelia, Anisa Gumerova, Kseniia Ievleva, Tan Chun Kuo, Funda Korkmaz, Vitaly Ryu, Alina Rahimova, Sakshi Gera, Charit Taneja, Ayesha Khan, Naseer Ahmad, Roberto Tamma, Zhuan Bian, Alberta Zallone, Se Min Kim, Maria I. NewJameel Iqbal, Tony Yuen, Mone Zaidi

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

The primitive neurohypophyseal nonapeptide oxytocin (OXT) has established functions in parturition, lactation, appetite, and social behavior. We have shown that OXT has direct actions on the mammalian skeleton, stimulating bone formation by osteoblasts and modulating the genesis and function of bone-resorbing osteoclasts. We deleted OXT receptors (OXTRs) selectively in osteoblasts and osteoclasts using Col2.3Cre and Acp5Cremice, respectively. Both male and female Col2.3Cre+:Oxtrfl/fl mice recapitulate the low-bone mass phenotype of Oxtr+/- mice, suggesting that OXT has a prominent osteoblastic action in vivo. Furthermore, abolishment of the anabolic effect of estrogen in Col2.3Cre+:Oxtrfl/fl mice suggests that osteoblastic OXTRs are necessary for estrogen action. In addition, the high bone mass in Acp5Cre+:Oxtrfl/fl mice indicates a prominent action of OXT in stimulating osteoclastogenesis. In contrast, we found that in pregnant and lactating Col2.3Cre+:Oxtrfl/fl mice, elevated OXT inhibits bone resorption and rescues the bone loss otherwise noted during pregnancy and lactation. However, OXT does not contribute to ovariectomy-induced bone loss. Finally, we show that OXT acts directly on OXTRs on adipocytes to suppress the whiteto- beige transition gene program. Despite this direct antibeiging action, injected OXT reduces total body fat, likely through an action on OXT-ergic neurons. Consistent with an antiobesity action of OXT, Oxt-/- and Oxtr-/- mice display increased total body fat. Overall, the actions of OXT on bone mass and body composition provide the framework for future therapies for osteoporosis and obesity.

Original languageEnglish
Pages (from-to)26808-26815
Number of pages8
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number52
DOIs
StatePublished - 26 Dec 2019

Keywords

  • Adipose tissue
  • Bone phenotype
  • Conditional knockout
  • Pituitary hormone

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