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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Journal Experts
2023
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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. |
format | Online Article Text |
id | pubmed-10402269 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Journal Experts |
record_format | MEDLINE/PubMed |
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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