Protein Tyrosine Phosphatase Receptor δ Serves As the Orexigenic Asprosin Receptor

Overview

Journal Cell Metab

Publisher Cell Press

Specialties Cell Biology
Endocrinology

Date 2022 Mar 17

PMID 35298903

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

Affiliations

Soon will be listed here.

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.

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