The Hypothalamic Glucagon-Like Peptide 1 Receptor Is Sufficient but Not Necessary for the Regulation of Energy Balance and Glucose Homeostasis in Mice
| العنوان: | The Hypothalamic Glucagon-Like Peptide 1 Receptor Is Sufficient but Not Necessary for the Regulation of Energy Balance and Glucose Homeostasis in Mice |
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| المؤلفون: | Jacob D. Brown, Randy J. Seeley, Adriana Landivar-Rocha, Hannah Smouse, Darleen A. Sandoval, Jennifer E. Ayala, Julio E. Ayala, Melissa A. Burmeister, Doris A. Stoffers, Daniel J. Drucker |
| المصدر: | Diabetes |
| بيانات النشر: | American Diabetes Association, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, endocrine system, medicine.medical_specialty, Pro-Opiomelanocortin, Endocrinology, Diabetes and Metabolism, Hypothalamus, Carbohydrate metabolism, Diet, High-Fat, Weight Gain, Incretins, Glucagon-Like Peptide-1 Receptor, Eating, Mice, 03 medical and health sciences, Proopiomelanocortin, Glucagon-Like Peptide 1, Internal medicine, Internal Medicine, medicine, Animals, Homeostasis, Glucose homeostasis, Neurons, 2. Zero hunger, Glucose tolerance test, medicine.diagnostic_test, biology, Venoms, Liraglutide, digestive, oral, and skin physiology, Glucose Tolerance Test, Glucose, Metabolism, 030104 developmental biology, Endocrinology, Gene Knockdown Techniques, Body Composition, Anorectic, biology.protein, Exenatide, Energy Metabolism, Peptides, hormones, hormone substitutes, and hormone antagonists, Paraventricular Hypothalamic Nucleus, medicine.drug |
| الوصف: | Pharmacological activation of the hypothalamic glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) promotes weight loss and improves glucose tolerance. This demonstrates that the hypothalamic GLP-1R is sufficient but does not show whether it is necessary for the effects of exogenous GLP-1R agonists (GLP-1RA) or endogenous GLP-1 on these parameters. To address this, we crossed mice harboring floxed Glp1r alleles to mice expressing Nkx2.1-Cre to knock down Glp1r expression throughout the hypothalamus (GLP-1RKDΔNkx2.1cre). We also generated mice lacking Glp1r expression specifically in two GLP-1RA–responsive hypothalamic feeding nuclei/cell types, the paraventricular nucleus (GLP-1RKDΔSim1cre) and proopiomelanocortin neurons (GLP-1RKDΔPOMCcre). Chow-fed GLP-1RKDΔNkx2.1cre mice exhibited increased food intake and energy expenditure with no net effect on body weight. When fed a high-fat diet, these mice exhibited normal food intake but elevated energy expenditure, yielding reduced weight gain. None of these phenotypes were observed in GLP-1RKDΔSim1cre and GLP-1RKDΔPOMCcre mice. The acute anorectic and glucose tolerance effects of peripherally dosed GLP-1RA exendin-4 and liraglutide were preserved in all mouse lines. Chronic liraglutide treatment reduced body weight in chow-fed GLP-1RKDΔNkx2.1cre mice, but this effect was attenuated with high-fat diet feeding. In sum, classic homeostatic control regions are sufficient but not individually necessary for the effects of GLP-1RA on nutrient homeostasis. |
| تدمد: | 1939-327X 0012-1797 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::433a6a4cd9a77974745102fd8d93d586Test https://doi.org/10.2337/db16-1102Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....433a6a4cd9a77974745102fd8d93d586 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1939327X 00121797 |
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