Researchers identify potential new treatment for metabolic syndrome


Date:
April 11, 2022
Source:
University Hospitals Cleveland Medical Center
Summary:
Metabolic syndrome increases a person's risk for diabetes, heart
disease, and stroke, and includes conditions such as obesity, high
blood pressure and high blood sugar. In a recent mouse-model study,
researchers have furthered their progress to develop a drug to
treat metabolic syndrome by identifying a receptor that controls
appetite and body weight.



FULL STORY ========================================================================== Metabolic syndrome increases a person's risk for diabetes, heart disease,
and stroke, and includes conditions such as obesity, high blood pressure
and high blood sugar. In a recent mouse-model study, published in Cell Metabolism, researchers at University Hospitals (UH), Harrington Discovery Institute at UH, and Case Western Reserve University have furthered their progress to develop a drug to treat metabolic syndrome by identifying
a receptor that controls appetite and body weight.


==========================================================================
"In 2016, our lab discovered a hormone called asprosin, which stimulates appetite and increases blood glucose levels by acting on the hypothalamus
and the liver," explained Atul Chopra, MD, PhD, senior author on the
study, Investigator at the Harrington Discovery Institute and Associate Director of the Oxford-Harrington Rare Disease Center, Attending Medical Geneticist at UH, and Associate Professor of Medicine, and Genetics
and Genomics at Case Western Reserve School of Medicine. "Individuals
that have low blood asprosin levels don't feel hunger like others
do and have lower glucose and insulin levels." Asprosin stimulates
appetite by activating key "hunger" neurons of the brain, called AgRP
neurons. Asprosin works by binding a protein on the neuron surface called
a "receptor." To better understand how receptors work, one might use a key
and lock analogy, where a hormone is a key, and its receptor is the lock.

"By using a sophisticated technique called mass spectrometry, we
identified protein tyrosine phosphatase receptor ? (Ptprd) as the
receptor for asprosin," said Ila Mishra, PhD, first author on the study
and research associate at Harrington Discovery Institute and Case Western Reserve School of Medicine.

"Genetic deletion of Ptprd in mice reduced appetite and body weight,
rendering mice unresponsive to asprosin's appetite stimulating effect. In
other words, Ptprd is necessary for asprosin-mediated appetite
stimulation. This result is the crux of our discovery. A receptor
is necessary for a hormone to work, and in the case of asprosin's
ability to control appetite and body weight, that receptor is Ptprd."
The identity of the receptor that allows asprosin to activate AgRP
neurons and stimulate appetite was previously a mystery, and this gap
in knowledge was a barrier to fully understanding how this hormone works.

Since the discovery of asprosin, many studies have shown that blood
asprosin levels are elevated in patients with metabolic syndrome, leading
to weight gain and high blood sugar. The research team has also seen
that reduced blood asprosin levels lead to protection from metabolic
syndrome by suppressing appetite and blood sugar.

"The identification of Ptprd as an asprosin receptor provided us an
opportunity to develop a new therapeutic against 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
suppressed appetite, body weight and blood glucose levels in obese mice
by sequestering plasma asprosin.

From a clinical standpoint, it means that this discovery could
potentially yield a brand-new drug against metabolic syndrome."
"Further, we believe that asprosin performs many more functions in
addition to appetite stimulation," added Dr. Mishra. "Identifying these
new functions is the next step in our research." The team also plans
to study intracellular mechanisms involved in asprosin- Ptprd signaling,
and simultaneously develop the Ptprd receptor trap for potential use in patients with metabolic syndrome.


========================================================================== Story Source: Materials provided by University_Hospitals_Cleveland_Medical_Center. Note: Content may be
edited for style and length.


========================================================================== Journal Reference:
1. 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 d serves as the orexigenic
asprosin receptor. Cell Metabolism, 2022; 34 (4): 549 DOI:
10.1016/j.cmet.2022.02.012 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/04/220411113720.htm

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