"In 2016, our lab discovered a hormone called asprosone that stimulates appetite and raises blood sugar levels by acting on the hypothalamus and liver," said Harlem, MD, PhD, senior author of the study.
Atul Chopra, a researcher at the Dayton Discovery Institute, associate director of the Oxford-Harrington Centre for Rare Diseases, attending medical geneticist at UH and associate professor of medicine, genetics and genomics at Case Western Reserve School of Medicine, explained
.
"People with lower levels of aswanin in their blood don't feel as hungry as others and have lower blood sugar and insulin levels
.
"
Asprosin stimulates appetite by activating key "hunger" neurons in the brain, called AgRP neurons
.
Aswan proteins work by binding to proteins called "receptors" on the surface of neurons
.
To better understand how the receptors work, we can use the key and lock analogy, where the hormone is the key and its receptor is the lock
.
"By using a complex technique called mass spectrometry, we identified the protein tyrosine phosphatase receptor? Ila Mishra, first author of the study and associate investigator at the Harrington Institute for Discovery and Case Western Reserve School of Medicine "
Deletion of the Ptprd gene in mice reduces appetite and body weight, making the mice unresponsive to the appetite-stimulating effects
of asprin.
In other words, Ptprd is necessary for asprin-mediated appetite stimulation," said
Dr.
This result is the key to our discovery
.
The receptor is required for the hormone to work, and in the case of asprosin that controls appetite and weight, that receptor is Ptprd
.
"
The identity of the receptor that allows asprosol to activate AgRP neurons and stimulate appetite was previously a mystery, and this knowledge gap is an obstacle to a comprehensive understanding of how the hormone works
.
Since the discovery of aswan protein, many studies have shown that people with metabolic syndrome have elevated levels of aswan protein in their blood, leading to weight gain and hyperglycemia
.
The team also found that reducing blood levels of alanine protease can suppress appetite and blood sugar, thereby preventing metabolic syndrome
.
"The identification of Ptprd as an asprosin receptor provides us with an opportunity to develop a new approach to the treatment of metabolic syndrome," said Dr.
Chopra
.
"We used the discovery of the asprosin receptor to develop a new drug called a receptor trap," explained Dr.
Mishra
.
"This new drug suppresses appetite, body weight in obese mice by sequestering plasma aswan proteins.
and blood sugar levels
.
From a clinical standpoint, this means that this discovery could lead to a whole new class of drugs for metabolic syndrome
.
"
"Furthermore, we believe that asprosol has many other functions besides stimulating appetite," added Dr.
Mishra
.
"Identifying these new functions is the next step in our research
.
"
The team also plans to study the intracellular mechanisms involved in asprosin-Ptprd signaling, while developing Ptprd receptor traps for use in patients with metabolic syndrome
.
Journal Reference :
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.
Protein tyrosine phosphatase receptor δ serves as the orexigenic asprosin receptor .
Cell Metabolism , 2022; 34 (4): 549 DOI: 10.
1016/j.
cmet.
2022.
02.
012
