Back to Search
Start Over
Gpr17 in AgRP Neurons Regulates Feeding and Sensitivity to Insulin and Leptin
- Source :
- Diabetes
- Publication Year :
- 2015
- Publisher :
- American Diabetes Association, 2015.
-
Abstract
- Hypothalamic neurons expressing agouti-related peptide (AgRP) regulate eating and glucose metabolism. Ablation of FOXO1 in AgRP neurons of mice results in reduced food intake, leanness, improved glucose homeostasis, and increased sensitivity to insulin and leptin. We tentatively identified G-protein–coupled receptor Gpr17 as an effector of FOXO1 orexigenic signals in AgRP neurons. In this study, we generated and characterized AgRP neuron–specific Gpr17 knockout mice (Agrp-Gpr17−/−) to test the hypothesis that Gpr17 regulates appetite, energy expenditure, and metabolism. Agrp-Gpr17−/− mice show reduced food intake, increased relative energy expenditure, and increased satiety, resulting in leanness and reduced body fat. They also show increased central nervous system sensitivity to insulin and leptin and reduced plasma glucose excursions following the administration of glucose or pyruvate. In summary, AgRP neuron–specific Gpr17 knockouts phenocopy FOXO1 knockouts in the same cell type, thus supporting our original hypothesis and providing further impetus to develop Gpr17 antagonists for the treatment of obesity.
- Subjects :
- Leptin
Male
medicine.medical_specialty
Endocrinology, Diabetes and Metabolism
media_common.quotation_subject
medicine.medical_treatment
Hypothalamus
Nerve Tissue Proteins
FOXO1
Biology
Carbohydrate metabolism
Receptors, G-Protein-Coupled
Eating
Mice
Orexigenic
Internal medicine
Internal Medicine
medicine
Animals
Glucose homeostasis
Agouti-Related Protein
media_common
Mice, Knockout
Neurons
2. Zero hunger
Insulin
digestive, oral, and skin physiology
Appetite
Metabolism
Endocrinology
nervous system
Knockout mouse
Body Composition
Insulin Resistance
Energy Metabolism
hormones, hormone substitutes, and hormone antagonists
medicine.drug
Subjects
Details
- ISSN :
- 1939327X and 00121797
- Volume :
- 64
- Database :
- OpenAIRE
- Journal :
- Diabetes
- Accession number :
- edsair.doi.dedup.....15bd472025ea47f7700b5b5a23df4951
- Full Text :
- https://doi.org/10.2337/db15-0390