Ghrelin Receptor Signaling Is Not Required for Glucocorticoid-Induced Obesity in Male Mice
| Autor: | Alexander Edwards, Lindsay Hyland, David MacDonald, Alfonso Abizaid, Ilia N. Karatsoreos, Marianne O. Klein, Rebecca E Hay, Matthew N. Hill |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
medicine.medical_specialty endocrine system medicine.drug_class Glycine Prefrontal Cortex Weight Gain Hippocampus 03 medical and health sciences chemistry.chemical_compound Eating Mice 0302 clinical medicine Endocrinology Corticosterone Internal medicine medicine Animals Obesity Receptor Receptors Ghrelin Glucocorticoids Research Articles 030304 developmental biology Adiposity 2. Zero hunger Mice Knockout 0303 health sciences Glucose tolerance test medicine.diagnostic_test business.industry digestive oral and skin physiology Triazoles Receptor antagonist 3. Good health Mice Inbred C57BL chemistry Ghrelin medicine.symptom business Weight gain 030217 neurology & neurosurgery Glucocorticoid hormones hormone substitutes and hormone antagonists Hormone medicine.drug |
| Zdroj: | Endocrinology |
| Popis: | Chronically elevated levels of glucocorticoids increase food intake, weight gain, and adiposity. Similarly, ghrelin, a gut-secreted hormone, is also associated with weight gain, adiposity, and increased feeding. Here we sought to determine if corticosterone-induced metabolic and behavioral changes require functional ghrelin receptors (GHSR). To do this, we treated male C57BL mice with chronic corticosterone (CORT) mixed in their drinking water for 28 days. Half of these mice received the GHSR antagonist JMV2959 via osmotic minipumps while treated with CORT. In a second experiment, we gave the same CORT protocol to mice with a targeted mutation to the GHSR or their wild-type littermates. As expected, CORT treatment increased food intake, weight gain, and adiposity, but contrary to expectations, mice treated with a GHSR receptor antagonist or GHSR knockout (KO) mice did not show attenuated food intake, weight gain, or adiposity in response to CORT. Similarly, the effects of CORT on the liver were the same or more pronounced in GHSR antagonist-treated and GHSR KO mice. Treatment with JMV2959 did attenuate the effects of chronic CORT on glycemic regulation as determined by the glucose tolerance test. Finally, disruption of GHSR signaling resulted in behavioral responses associated with social withdrawal, potentially due to neuroprotective effects of GHSR activation. In all, we propose that blocking GHSR signaling helps to moderate glucose concentrations when CORT levels are high, but blocking GHSR signaling does not prevent increased food intake, weight gain, or increased adiposity produced by chronic CORT. |
| Databáze: | OpenAIRE |
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