Cellular and synaptic reorganization of arcuate NPY/AgRP and POMC neurons after exercise

Objective: Hypothalamic Pro-opiomelanocortin (POMC) and Neuropeptide Y/Agouti-Related Peptide (NPY/AgRP) neurons are critical nodes of a circuit within the brain that sense key metabolic cues as well as regulate metabolism. Importantly, these neurons retain an innate ability to rapidly reorganize sy...

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Main Authors: Zhenyan He, Yong Gao, Amber L. Alhadeff, Carlos M. Castorena, Yiru Huang, Linh Lieu, Sadia Afrin, Jia Sun, J. Nicholas Betley, Hongbo Guo, Kevin W. Williams
Format: Article
Language:English
Published: Elsevier 2018-12-01
Series:Molecular Metabolism
Online Access:http://www.sciencedirect.com/science/article/pii/S2212877818308706
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author Zhenyan He
Yong Gao
Amber L. Alhadeff
Carlos M. Castorena
Yiru Huang
Linh Lieu
Sadia Afrin
Jia Sun
J. Nicholas Betley
Hongbo Guo
Kevin W. Williams
author_facet Zhenyan He
Yong Gao
Amber L. Alhadeff
Carlos M. Castorena
Yiru Huang
Linh Lieu
Sadia Afrin
Jia Sun
J. Nicholas Betley
Hongbo Guo
Kevin W. Williams
author_sort Zhenyan He
collection DOAJ
description Objective: Hypothalamic Pro-opiomelanocortin (POMC) and Neuropeptide Y/Agouti-Related Peptide (NPY/AgRP) neurons are critical nodes of a circuit within the brain that sense key metabolic cues as well as regulate metabolism. Importantly, these neurons retain an innate ability to rapidly reorganize synaptic inputs and electrophysiological properties in response to metabolic state. While the cellular properties of these neurons have been investigated in the context of obesity, much less is known about the effects of exercise training. Methods: In order to further investigate this issue, we utilized neuron-specific transgenic mouse models to identify POMC and NPY/AgRP neurons for patch-clamp electrophysiology experiments. Results: Using whole-cell patch-clamp electrophysiology, we found exercise depolarized and increased firing rate of arcuate POMC neurons. The increased excitability of POMC neurons was concomitant with increased excitatory inputs to these neurons. In agreement with recent work suggesting leptin plays an important role in the synaptic (re)organization of POMC neurons, POMC neurons which express leptin receptors were more sensitive to exercise-induced changes in biophysical properties. Opposite to effects observed in POMC neurons, NPY neurons were shunted toward inhibition following exercise. Conclusions: Together, these data support a rapid reorganization of synaptic inputs and biophysical properties in response to exercise, which may facilitate adaptations to altered energy balance and glucose metabolism. Keywords: Melanocortin, Energy balance, Leptin receptor, Exercise, Patch-clamp, Electrophysiology
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spelling doaj.art-c762c1827ad341e28080b5491013516e2022-12-21T17:45:40ZengElsevierMolecular Metabolism2212-87782018-12-0118107119Cellular and synaptic reorganization of arcuate NPY/AgRP and POMC neurons after exerciseZhenyan He0Yong Gao1Amber L. Alhadeff2Carlos M. Castorena3Yiru Huang4Linh Lieu5Sadia Afrin6Jia Sun7J. Nicholas Betley8Hongbo Guo9Kevin W. Williams10The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China; Division of Hypothalamic Research, Department of Internal Medicine, the University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USADivision of Hypothalamic Research, Department of Internal Medicine, the University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA; National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, ChinaDepartment of Biology, University of Pennsylvania, Philadelphia, PA, 19104, USADivision of Hypothalamic Research, Department of Internal Medicine, the University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USAThe National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China; Division of Hypothalamic Research, Department of Internal Medicine, the University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USADivision of Hypothalamic Research, Department of Internal Medicine, the University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USADivision of Hypothalamic Research, Department of Internal Medicine, the University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USADivision of Hypothalamic Research, Department of Internal Medicine, the University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USADepartment of Biology, University of Pennsylvania, Philadelphia, PA, 19104, USAThe National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, ChinaDivision of Hypothalamic Research, Department of Internal Medicine, the University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA; Corresponding author. University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX, 75390-9077, USA.Objective: Hypothalamic Pro-opiomelanocortin (POMC) and Neuropeptide Y/Agouti-Related Peptide (NPY/AgRP) neurons are critical nodes of a circuit within the brain that sense key metabolic cues as well as regulate metabolism. Importantly, these neurons retain an innate ability to rapidly reorganize synaptic inputs and electrophysiological properties in response to metabolic state. While the cellular properties of these neurons have been investigated in the context of obesity, much less is known about the effects of exercise training. Methods: In order to further investigate this issue, we utilized neuron-specific transgenic mouse models to identify POMC and NPY/AgRP neurons for patch-clamp electrophysiology experiments. Results: Using whole-cell patch-clamp electrophysiology, we found exercise depolarized and increased firing rate of arcuate POMC neurons. The increased excitability of POMC neurons was concomitant with increased excitatory inputs to these neurons. In agreement with recent work suggesting leptin plays an important role in the synaptic (re)organization of POMC neurons, POMC neurons which express leptin receptors were more sensitive to exercise-induced changes in biophysical properties. Opposite to effects observed in POMC neurons, NPY neurons were shunted toward inhibition following exercise. Conclusions: Together, these data support a rapid reorganization of synaptic inputs and biophysical properties in response to exercise, which may facilitate adaptations to altered energy balance and glucose metabolism. Keywords: Melanocortin, Energy balance, Leptin receptor, Exercise, Patch-clamp, Electrophysiologyhttp://www.sciencedirect.com/science/article/pii/S2212877818308706
spellingShingle Zhenyan He
Yong Gao
Amber L. Alhadeff
Carlos M. Castorena
Yiru Huang
Linh Lieu
Sadia Afrin
Jia Sun
J. Nicholas Betley
Hongbo Guo
Kevin W. Williams
Cellular and synaptic reorganization of arcuate NPY/AgRP and POMC neurons after exercise
Molecular Metabolism
title Cellular and synaptic reorganization of arcuate NPY/AgRP and POMC neurons after exercise
title_full Cellular and synaptic reorganization of arcuate NPY/AgRP and POMC neurons after exercise
title_fullStr Cellular and synaptic reorganization of arcuate NPY/AgRP and POMC neurons after exercise
title_full_unstemmed Cellular and synaptic reorganization of arcuate NPY/AgRP and POMC neurons after exercise
title_short Cellular and synaptic reorganization of arcuate NPY/AgRP and POMC neurons after exercise
title_sort cellular and synaptic reorganization of arcuate npy agrp and pomc neurons after exercise
url http://www.sciencedirect.com/science/article/pii/S2212877818308706
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