A leptin-regulated circuit controls glucose mobilization during noxious stimuli
| Autor: | Maja Joosten, Martin G. Myers, Paulette B. Goforth, John M. Hayes, Warren Pan, Christa M. Patterson, Deanna M. Arble, Thomas Lanigan, Jamie Sacksner, Kamal Rahmouni, Eva L. Feldman, Margaret B. Allison, Jonathan N. Flak, Donald A. Morgan, David P. Olson, Randy J. Seeley |
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| Rok vydání: | 2017 |
| Předmět: |
Blood Glucose
Leptin Male 0301 basic medicine Sympathetic nervous system medicine.medical_specialty Sympathetic Nervous System Population Pain Carbohydrate metabolism Periaqueductal gray Mice 03 medical and health sciences 0302 clinical medicine Internal medicine Adipocytes medicine Noxious stimulus Animals Receptor education Mice Knockout Neurons Glucose tolerance test education.field_of_study Behavior Animal medicine.diagnostic_test Chemistry Brain General Medicine Glucose Tolerance Test Mice Inbred C57BL Glucose Phenotype 030104 developmental biology medicine.anatomical_structure Endocrinology nervous system Hyperglycemia Receptors Leptin Female Proto-Oncogene Proteins c-fos 030217 neurology & neurosurgery Research Article |
| Zdroj: | Journal of Clinical Investigation. 127:3103-3113 |
| ISSN: | 1558-8238 0021-9738 |
| DOI: | 10.1172/jci90147 |
| Popis: | Adipocytes secrete the hormone leptin to signal the sufficiency of energy stores. Reductions in circulating leptin concentrations reflect a negative energy balance, which augments sympathetic nervous system (SNS) activation in response to metabolically demanding emergencies. This process ensures adequate glucose mobilization despite low energy stores. We report that leptin receptor-expressing neurons (LepRb neurons) in the periaqueductal gray (PAG), the largest population of LepRb neurons in the brain stem, mediate this process. Application of noxious stimuli, which often signal the need to mobilize glucose to support an appropriate response, activated PAG LepRb neurons, which project to and activate parabrachial nucleus (PBN) neurons that control SNS activation and glucose mobilization. Furthermore, activating PAG LepRb neurons increased SNS activity and blood glucose concentrations, while ablating LepRb in PAG neurons augmented glucose mobilization in response to noxious stimuli. Thus, decreased leptin action on PAG LepRb neurons augments the autonomic response to noxious stimuli, ensuring sufficient glucose mobilization during periods of acute demand in the face of diminished energy stores. |
| Databáze: | OpenAIRE |
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