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J Clin Invest. 2017 Aug 1;127(8):3103-3113. doi: 10.1172/JCI90147. Epub 2017 Jul 17.

A leptin-regulated circuit controls glucose mobilization during noxious stimuli.

Author information

1
Department of Internal Medicine.
2
Department of Surgery.
3
Graduate Program in Cellular and Molecular Biology, and.
4
Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA.
5
Radboud University, Nijmegen, Netherlands.
6
Department of Pharmacology, University of Iowa, Iowa City, Iowa, USA.
7
Department of Molecular and Integrative Physiology.
8
Department of Neurology, and.
9
Division of Endocrinology, Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan, USA.

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.

PMID:
28714862
PMCID:
PMC5531403
DOI:
10.1172/JCI90147
[Indexed for MEDLINE]
Free PMC Article

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