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G Protein-Coupled Receptor 17 (Gpr17) Enhances Leptin and Insulin Sensitivity in Lean and Obese Mouse Models
Xun Sun1,2,3, Connor Mahler4, Natalie D Stull5
1Herman B Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Obesity (Silver Spring, Md.)
|May 14, 2026
Summary
Removing G protein-coupled receptor 17 (Gpr17) improves energy balance and glucose metabolism. Gpr17 knockout mice show enhanced insulin and leptin sensitivity, suggesting Gpr17 as a therapeutic target for obesity.
Area of Science:
- Metabolic research
- Endocrinology
- Obesity research
Background:
- Obesity drives diabetes and is linked to insulin and leptin resistance.
- Previous studies indicated Gpr17 loss in specific neurons/intestine improves energy balance.
- Gpr17's role in systemic insulin and leptin sensitivity requires further investigation.
Purpose of the Study:
- To determine if general Gpr17 loss enhances insulin and leptin sensitivity.
- To investigate the metabolic effects of germline Gpr17 knockout.
Main Methods:
- Generated germline Gpr17 knockout mice on lean and obese backgrounds.
- Characterized the metabolic profile of Gpr17 knockout mice.
- Utilized euglycemic-hyperinsulinemic clamp studies.
Main Results:
- Gpr17 knockout mice displayed increased energy expenditure and oxygen consumption.
- Enhanced insulin sensitivity was observed, with increased glycogen synthesis and reduced glycolysis.
- Obese Gpr17 knockout mice showed improved insulin sensitivity, reduced baseline insulin, and enhanced leptin response.
Conclusions:
- Gpr17 inhibits insulin and leptin sensitivity.
- Gpr17 represents a potential therapeutic target for obesity and related metabolic disorders.
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