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Interplay between glucose and leptin signaling determines the strength of GABAergic synapses at POMC neurons
Regulation of GABAergic inhibitory inputs and alterations in POMC neuron activity by nutrients and adiposity signals regulate energy and glucose homeostasis. Thus, understanding how POMC neurons integrate these two signal molecules at the synaptic level is important. Here we show that leptin’s actio...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375782/ https://www.ncbi.nlm.nih.gov/pubmed/25808323 http://dx.doi.org/10.1038/ncomms7618 |
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author | Lee, Dong Kun Jeong, Jae Hoon Chun, Sung-Kun Chua, Streamson Jo, Young-Hwan |
author_facet | Lee, Dong Kun Jeong, Jae Hoon Chun, Sung-Kun Chua, Streamson Jo, Young-Hwan |
author_sort | Lee, Dong Kun |
collection | PubMed |
description | Regulation of GABAergic inhibitory inputs and alterations in POMC neuron activity by nutrients and adiposity signals regulate energy and glucose homeostasis. Thus, understanding how POMC neurons integrate these two signal molecules at the synaptic level is important. Here we show that leptin’s action on GABA release to POMC neurons is influenced by glucose levels. Leptin stimulates the JAK2-PI3K pathway in both presynaptic GABAergic terminals and postsynaptic POMC neurons. Inhibition of AMPK activity in presynaptic terminals decreases GABA release at 10 mM glucose. However, postsynaptic TRPC channel opening by the PI3K-PLC signaling pathway in POMC neurons enhances spontaneous GABA release via activation of presynaptic MC3/4 and mGlu receptors at 2.5 mM glucose. High-fat feeding blunts AMPK-dependent presynaptic inhibition, whereas PLC-mediated GABAergic feedback inhibition remains responsive to leptin. Our data indicate that the interplay between glucose and leptin signaling in glutamatergic POMC neurons is critical for determining the strength of inhibitory tone towards POMC neurons. |
format | Online Article Text |
id | pubmed-4375782 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
record_format | MEDLINE/PubMed |
spelling | pubmed-43757822015-09-26 Interplay between glucose and leptin signaling determines the strength of GABAergic synapses at POMC neurons Lee, Dong Kun Jeong, Jae Hoon Chun, Sung-Kun Chua, Streamson Jo, Young-Hwan Nat Commun Article Regulation of GABAergic inhibitory inputs and alterations in POMC neuron activity by nutrients and adiposity signals regulate energy and glucose homeostasis. Thus, understanding how POMC neurons integrate these two signal molecules at the synaptic level is important. Here we show that leptin’s action on GABA release to POMC neurons is influenced by glucose levels. Leptin stimulates the JAK2-PI3K pathway in both presynaptic GABAergic terminals and postsynaptic POMC neurons. Inhibition of AMPK activity in presynaptic terminals decreases GABA release at 10 mM glucose. However, postsynaptic TRPC channel opening by the PI3K-PLC signaling pathway in POMC neurons enhances spontaneous GABA release via activation of presynaptic MC3/4 and mGlu receptors at 2.5 mM glucose. High-fat feeding blunts AMPK-dependent presynaptic inhibition, whereas PLC-mediated GABAergic feedback inhibition remains responsive to leptin. Our data indicate that the interplay between glucose and leptin signaling in glutamatergic POMC neurons is critical for determining the strength of inhibitory tone towards POMC neurons. 2015-03-26 /pmc/articles/PMC4375782/ /pubmed/25808323 http://dx.doi.org/10.1038/ncomms7618 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Lee, Dong Kun Jeong, Jae Hoon Chun, Sung-Kun Chua, Streamson Jo, Young-Hwan Interplay between glucose and leptin signaling determines the strength of GABAergic synapses at POMC neurons |
title | Interplay between glucose and leptin signaling determines the strength of GABAergic synapses at POMC neurons |
title_full | Interplay between glucose and leptin signaling determines the strength of GABAergic synapses at POMC neurons |
title_fullStr | Interplay between glucose and leptin signaling determines the strength of GABAergic synapses at POMC neurons |
title_full_unstemmed | Interplay between glucose and leptin signaling determines the strength of GABAergic synapses at POMC neurons |
title_short | Interplay between glucose and leptin signaling determines the strength of GABAergic synapses at POMC neurons |
title_sort | interplay between glucose and leptin signaling determines the strength of gabaergic synapses at pomc neurons |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375782/ https://www.ncbi.nlm.nih.gov/pubmed/25808323 http://dx.doi.org/10.1038/ncomms7618 |
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