Protein tyrosine phosphatase receptor δ serves as the orexigenic asprosin receptor

Ila Mishra, Wei Rose Xie, Juan C. Bournat, Yang He, Chunmei Wang, Elizabeth Sabath Silva, Hailan Liu, Zhiqiang Ku, Yinghua Chen, Bernadette O. Erokwu, Peilin Jia, Zhongming Zhao, Zhiqiang An, Chris A. Flask, Yanlin He, Yong Xu, Atul R. Chopra

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Asprosin is a fasting-induced glucogenic and centrally acting orexigenic hormone. The olfactory receptor Olfr734 is known to be the hepatic receptor for asprosin that mediates its effects on glucose production, but the receptor for asprosin's orexigenic function has been unclear. Here, we have identified protein tyrosine phosphatase receptor δ (Ptprd) as the orexigenic receptor for asprosin. Asprosin functions as a high-affinity Ptprd ligand in hypothalamic AgRP neurons, regulating the activity of this circuit in a cell-autonomous manner. Genetic ablation of Ptprd results in a strong loss of appetite, leanness, and an inability to respond to the orexigenic effects of asprosin. Ablation of Ptprd specifically in AgRP neurons causes resistance to diet-induced obesity. Introduction of the soluble Ptprd ligand-binding domain in the circulation of mice suppresses appetite and blood glucose levels by sequestering plasma asprosin. Identification of Ptprd as the orexigenic asprosin receptor creates a new avenue for the development of anti-obesity therapeutics.

Original languageEnglish
Pages (from-to)549-563.e8
JournalCell Metabolism
Issue number4
StatePublished - Apr 5 2022

Bibliographical note

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© 2022 Elsevier Inc.


  • AgRP
  • Ptprd
  • appetite
  • asprosin
  • hypothalamus
  • metabolism
  • obesity
  • receptor

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology


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