Protein tyrosine phosphatase receptor δ serves as the orexigenic asprosin receptor.

Abstract

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.

• Authors: 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
• Journal: Cell metabolism (Cell Metab) Vol. 34 Issue 4 Pg. 549-563.e8 (04 05 2022) ISSN: 1932-7420 [Electronic] United States
• PMID: 35298903 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2022 Elsevier Inc. All rights reserved.

Chemical References

• Agouti-Related Protein
• Fibrillin-1
• Ligands
• Peptide Fragments
• Peptide Hormones
• asprosin protein, mouse
• Ptprd protein, mouse
• Receptor-Like Protein Tyrosine Phosphatases, Class 2
• Glucose

Topics

• Agouti-Related Protein
• Animals
• Fibrillin-1 (metabolism)
• Glucose (metabolism)
• Ligands
• Mice
• Obesity (metabolism)
• Peptide Fragments (metabolism)
• Peptide Hormones (genetics, metabolism)
• Receptor-Like Protein Tyrosine Phosphatases, Class 2 (metabolism)