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Competition between stochastic neuropeptide signals calibrates the rate of satiation

We investigated how transmission of hunger- and satiety-promoting neuropeptides, NPY and αMSH, is integrated at the level of intracellular signaling to control feeding. Receptors for these peptides use the second messenger cAMP. How cAMP integrates opposing peptide signals to regulate energy balance...

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Autores principales: Zhang, Stephen X., Kim, Angela, Madara, Joseph C., Zhu, Paula K., Christenson, Lauren F., Lutas, Andrew, Kalugin, Peter N., Jin, Yihan, Pal, Akash, Tian, Lin, Lowell, Bradford B., Andermann, Mark L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Journal Experts 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10402269/
https://www.ncbi.nlm.nih.gov/pubmed/37546985
http://dx.doi.org/10.21203/rs.3.rs-3185572/v1
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author Zhang, Stephen X.
Kim, Angela
Madara, Joseph C.
Zhu, Paula K.
Christenson, Lauren F.
Lutas, Andrew
Kalugin, Peter N.
Jin, Yihan
Pal, Akash
Tian, Lin
Lowell, Bradford B.
Andermann, Mark L.
author_facet Zhang, Stephen X.
Kim, Angela
Madara, Joseph C.
Zhu, Paula K.
Christenson, Lauren F.
Lutas, Andrew
Kalugin, Peter N.
Jin, Yihan
Pal, Akash
Tian, Lin
Lowell, Bradford B.
Andermann, Mark L.
author_sort Zhang, Stephen X.
collection PubMed
description We investigated how transmission of hunger- and satiety-promoting neuropeptides, NPY and αMSH, is integrated at the level of intracellular signaling to control feeding. Receptors for these peptides use the second messenger cAMP. How cAMP integrates opposing peptide signals to regulate energy balance, and the in vivo spatiotemporal dynamics of endogenous peptidergic signaling, remain largely unknown. We show that AgRP axon stimulation in the paraventricular hypothalamus evokes probabilistic NPY release that triggers stochastic cAMP decrements in downstream MC4R-expressing neurons (PVH(MC4R)). Meanwhile, POMC axon stimulation triggers stochastic, αMSH-dependent cAMP increments. Release of either peptide impacts a ~100 μm diameter region, and when these peptide signals overlap, they compete to control cAMP. The competition is reflected by hunger-state-dependent differences in the amplitude and persistence of cAMP transients: hunger peptides are more efficacious in the fasted state, satiety peptides in the fed state. Feeding resolves the competition by simultaneously elevating αMSH release and suppressing NPY release, thereby sustaining elevated cAMP in PVH(MC4R) neurons. In turn, cAMP potentiates feeding-related excitatory inputs and promotes satiation across minutes. Our findings highlight how biochemical integration of opposing, quantal peptide signals during energy intake orchestrates a gradual transition between stable states of hunger and satiety.
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spelling pubmed-104022692023-08-05 Competition between stochastic neuropeptide signals calibrates the rate of satiation Zhang, Stephen X. Kim, Angela Madara, Joseph C. Zhu, Paula K. Christenson, Lauren F. Lutas, Andrew Kalugin, Peter N. Jin, Yihan Pal, Akash Tian, Lin Lowell, Bradford B. Andermann, Mark L. Res Sq Article We investigated how transmission of hunger- and satiety-promoting neuropeptides, NPY and αMSH, is integrated at the level of intracellular signaling to control feeding. Receptors for these peptides use the second messenger cAMP. How cAMP integrates opposing peptide signals to regulate energy balance, and the in vivo spatiotemporal dynamics of endogenous peptidergic signaling, remain largely unknown. We show that AgRP axon stimulation in the paraventricular hypothalamus evokes probabilistic NPY release that triggers stochastic cAMP decrements in downstream MC4R-expressing neurons (PVH(MC4R)). Meanwhile, POMC axon stimulation triggers stochastic, αMSH-dependent cAMP increments. Release of either peptide impacts a ~100 μm diameter region, and when these peptide signals overlap, they compete to control cAMP. The competition is reflected by hunger-state-dependent differences in the amplitude and persistence of cAMP transients: hunger peptides are more efficacious in the fasted state, satiety peptides in the fed state. Feeding resolves the competition by simultaneously elevating αMSH release and suppressing NPY release, thereby sustaining elevated cAMP in PVH(MC4R) neurons. In turn, cAMP potentiates feeding-related excitatory inputs and promotes satiation across minutes. Our findings highlight how biochemical integration of opposing, quantal peptide signals during energy intake orchestrates a gradual transition between stable states of hunger and satiety. American Journal Experts 2023-07-26 /pmc/articles/PMC10402269/ /pubmed/37546985 http://dx.doi.org/10.21203/rs.3.rs-3185572/v1 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
spellingShingle Article
Zhang, Stephen X.
Kim, Angela
Madara, Joseph C.
Zhu, Paula K.
Christenson, Lauren F.
Lutas, Andrew
Kalugin, Peter N.
Jin, Yihan
Pal, Akash
Tian, Lin
Lowell, Bradford B.
Andermann, Mark L.
Competition between stochastic neuropeptide signals calibrates the rate of satiation
title Competition between stochastic neuropeptide signals calibrates the rate of satiation
title_full Competition between stochastic neuropeptide signals calibrates the rate of satiation
title_fullStr Competition between stochastic neuropeptide signals calibrates the rate of satiation
title_full_unstemmed Competition between stochastic neuropeptide signals calibrates the rate of satiation
title_short Competition between stochastic neuropeptide signals calibrates the rate of satiation
title_sort competition between stochastic neuropeptide signals calibrates the rate of satiation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10402269/
https://www.ncbi.nlm.nih.gov/pubmed/37546985
http://dx.doi.org/10.21203/rs.3.rs-3185572/v1
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