Glucose Availability Predicts the Feeding Response to Ghrelin in Male Mice, an Effect Dependent on AMPK in AgRP Neurons
| Autor: | Zane B. Andrews, Mathieu Méquinion, Romana Stark, David Spanswick, Sarah S Ch'ng, Dong Kong, Sarah Kathleen Haas Lockie, Andrew J Lawrence |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Antimetabolites medicine.medical_treatment Hypothalamus Neuropeptide Gene Expression Biology AMP-Activated Protein Kinases Deoxyglucose 03 medical and health sciences Mice 0302 clinical medicine Endocrinology AMP-activated protein kinase Internal medicine medicine Animals Agouti-Related Protein Neuropeptide Y RNA Messenger Neurons Leptin Insulin digestive oral and skin physiology Arcuate Nucleus of Hypothalamus AMPK Feeding Behavior Neuropeptide Y receptor Ghrelin 030104 developmental biology Glucose Gene Knockdown Techniques biology.protein 030217 neurology & neurosurgery hormones hormone substitutes and hormone antagonists Research Article |
| Popis: | Metabolic feedback from the periphery to the brain results from a dynamic physiologic fluctuation of nutrients and hormones, including glucose and fatty acids, ghrelin, leptin, and insulin. The specific interactions between humoral factors and how they influence feeding is largely unknown. We hypothesized that acute glucose availability may alter how the brain responds to ghrelin, a hormonal signal of energy availability. Acute glucose administration suppressed a range of ghrelin-induced behaviors as well as gene expression changes in hypothalamic neuropeptide Y (NPY) and agouti-related peptide (AgRP) neurons after ghrelin administration. Knockdown of the energy-sensing molecule AMP-activated protein kinase (AMPK) in AgRP neurons resulted in loss of the glucose effect, and mice responded as though pretreated with saline. Conversely, 2-deoxyglucose (2-DG), which decreases glucose availability, potentiated ghrelin-induced feeding and increased hypothalamic NPY mRNA levels. AMPK knockdown did not alter the additive effect of 2-DG and ghrelin on feeding. Our findings support the idea that computation of energy status is dynamic, is informed by multiple signals, and responds to acute fluctuations in metabolic state. These observations are broadly relevant to the investigation of neuroendocrine control of feeding and highlight the underappreciated complexity of control within these systems. |
| Databáze: | OpenAIRE |
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