Journal article
A leptin-regulated circuit controls glucose mobilization during noxious stimuli
The Journal of clinical investigation, Vol.127(8), pp.3103-3113
08/01/2017
DOI: 10.1172/JCI90147
PMCID: PMC5531403
PMID: 28714862
Abstract
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.
Details
- Title: Subtitle
- A leptin-regulated circuit controls glucose mobilization during noxious stimuli
- Creators
- Jonathan N Flak - Department of Internal MedicineDeanna Arble - Department of SurgeryWarren Pan - Graduate Program in Cellular and Molecular Biology, andChrista Patterson - Department of Internal MedicineThomas Lanigan - Department of Internal MedicinePaulette B Goforth - Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, USAJamie Sacksner - Department of Internal MedicineMaja Joosten - Radboud University, Nijmegen, NetherlandsDonald A Morgan - Department of Pharmacology, University of Iowa, Iowa City, Iowa, USAMargaret B Allison - Department of Molecular and Integrative PhysiologyJohn Hayes - Department of Neurology, andEva Feldman - Department of Neurology, andRandy J Seeley - Department of SurgeryDavid P Olson - Division of Endocrinology, Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan, USAKamal Rahmouni - Department of Pharmacology, University of Iowa, Iowa City, Iowa, USAMartin G Myers Jr - Department of Molecular and Integrative Physiology
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.127(8), pp.3103-3113
- Publisher
- United States
- DOI
- 10.1172/JCI90147
- PMID
- 28714862
- PMCID
- PMC5531403
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Grant note
- P30 DK020572 / NIDDK NIH HHS T32 GM007863 / NIGMS NIH HHS T32 GM007315 / NIGMS NIH HHS R56 DK104999 / NIDDK NIH HHS P01 HL084207 / NHLBI NIH HHS R01 DK098853 / NIDDK NIH HHS F32 DK098833 / NIDDK NIH HHS R01 DK104999 / NIDDK NIH HHS
- Language
- English
- Date published
- 08/01/2017
- Academic Unit
- Iowa Neuroscience Institute; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040284002771
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