PUBLICATION
Ptprf is the conserved receptor for Asprosin's glucogenic effects in vertebrates
- Authors
- Liu, Z., Wang, P., Hu, Y., Zhang, N., Xu, L., Kang, T., Zhao, S., Zhao, D., Chan, C., Li, J.
- ID
- ZDB-PUB-260212-1
- Date
- 2026
- Source
- Cell Reports 45: 116974 (Journal)
- Registered Authors
- Li, Jianzhen
- Keywords
- CP: metabolism, CP: neuroscience, asprosin, glucose, human, insulin receptor, mouse, ptprf, zebrafish
- MeSH Terms
-
- Animals
- Fibrillin-1*/metabolism
- Glucose*/metabolism
- Humans
- Liver/metabolism
- Mice
- Mice, Knockout
- Protein Binding
- Receptor-Like Protein Tyrosine Phosphatases, Class 2*/genetics
- Receptor-Like Protein Tyrosine Phosphatases, Class 2*/metabolism
- Vertebrates/metabolism
- Zebrafish/metabolism
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- PubMed
- 41671088 Full text @ Cell Rep.
Citation
Liu, Z., Wang, P., Hu, Y., Zhang, N., Xu, L., Kang, T., Zhao, S., Zhao, D., Chan, C., Li, J. (2026) Ptprf is the conserved receptor for Asprosin's glucogenic effects in vertebrates. Cell Reports. 45:116974.
Abstract
Asprosin, a fasting-induced glucogenic hormone, plays a crucial role in maintaining glucose homeostasis; however, its receptor remains elusive. This study identifies protein tyrosine phosphatase receptor F (Ptprf) as the receptor mediating Asprosin's metabolic functions. Using zebrafish models, we demonstrate the evolutionary conservation of Asprosin's role in glucose metabolism. Through binding assays, we determined Ptprf as Asprosin's interacting receptor in zebrafish liver. Zebrafish possess two Ptprf paralogs (Ptprfa/b), both hepatically expressed and binding Asprosin with high affinity. The genetic ablation of ptprfa/b reduced basal glucose levels and eliminated Asprosin-induced hyperglycemia. Conversely, the overexpression of soluble Ptprf ligand-binding domains neutralized Asprosin's glucogenic effects. These findings were validated in mammals: Asprosin binds PTPRF in mice and humans, and Ptprf knockout mice showed a blunted response to Asprosin. Our results establish Ptprf as an evolutionarily conserved Asprosin receptor across vertebrates, providing mechanistic insights for developing therapies targeting this pathway for diabetes and obesity.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping