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Neuronal Expression of Glucosylceramide Synthase in Central Nervous System Regulates Body Weight and Energy Homeostasis
Hypothalamic neurons are main regulators of energy homeostasis. Neuronal function essentially depends on plasma membrane-located gangliosides. The present work demonstrates that hypothalamic integration of metabolic signals requires neuronal expression of glucosylceramide synthase (GCS; UDP-glucose:...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3595213/ https://www.ncbi.nlm.nih.gov/pubmed/23554574 http://dx.doi.org/10.1371/journal.pbio.1001506 |
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author | Nordström, Viola Willershäuser, Monja Herzer, Silke Rozman, Jan von Bohlen und Halbach, Oliver Meldner, Sascha Rothermel, Ulrike Kaden, Sylvia Roth, Fabian C. Waldeck, Clemens Gretz, Norbert de Angelis, Martin Hrabě Draguhn, Andreas Klingenspor, Martin Gröne, Hermann-Josef Jennemann, Richard |
author_facet | Nordström, Viola Willershäuser, Monja Herzer, Silke Rozman, Jan von Bohlen und Halbach, Oliver Meldner, Sascha Rothermel, Ulrike Kaden, Sylvia Roth, Fabian C. Waldeck, Clemens Gretz, Norbert de Angelis, Martin Hrabě Draguhn, Andreas Klingenspor, Martin Gröne, Hermann-Josef Jennemann, Richard |
author_sort | Nordström, Viola |
collection | PubMed |
description | Hypothalamic neurons are main regulators of energy homeostasis. Neuronal function essentially depends on plasma membrane-located gangliosides. The present work demonstrates that hypothalamic integration of metabolic signals requires neuronal expression of glucosylceramide synthase (GCS; UDP-glucose:ceramide glucosyltransferase). As a major mechanism of central nervous system (CNS) metabolic control, we demonstrate that GCS-derived gangliosides interacting with leptin receptors (ObR) in the neuronal membrane modulate leptin-stimulated formation of signaling metabolites in hypothalamic neurons. Furthermore, ganglioside-depleted hypothalamic neurons fail to adapt their activity (c-Fos) in response to alterations in peripheral energy signals. Consequently, mice with inducible forebrain neuron-specific deletion of the UDP-glucose:ceramide glucosyltransferase gene (Ugcg) display obesity, hypothermia, and lower sympathetic activity. Recombinant adeno-associated virus (rAAV)-mediated Ugcg delivery to the arcuate nucleus (Arc) significantly ameliorated obesity, specifying gangliosides as seminal components for hypothalamic regulation of body energy homeostasis. |
format | Online Article Text |
id | pubmed-3595213 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-35952132013-04-02 Neuronal Expression of Glucosylceramide Synthase in Central Nervous System Regulates Body Weight and Energy Homeostasis Nordström, Viola Willershäuser, Monja Herzer, Silke Rozman, Jan von Bohlen und Halbach, Oliver Meldner, Sascha Rothermel, Ulrike Kaden, Sylvia Roth, Fabian C. Waldeck, Clemens Gretz, Norbert de Angelis, Martin Hrabě Draguhn, Andreas Klingenspor, Martin Gröne, Hermann-Josef Jennemann, Richard PLoS Biol Research Article Hypothalamic neurons are main regulators of energy homeostasis. Neuronal function essentially depends on plasma membrane-located gangliosides. The present work demonstrates that hypothalamic integration of metabolic signals requires neuronal expression of glucosylceramide synthase (GCS; UDP-glucose:ceramide glucosyltransferase). As a major mechanism of central nervous system (CNS) metabolic control, we demonstrate that GCS-derived gangliosides interacting with leptin receptors (ObR) in the neuronal membrane modulate leptin-stimulated formation of signaling metabolites in hypothalamic neurons. Furthermore, ganglioside-depleted hypothalamic neurons fail to adapt their activity (c-Fos) in response to alterations in peripheral energy signals. Consequently, mice with inducible forebrain neuron-specific deletion of the UDP-glucose:ceramide glucosyltransferase gene (Ugcg) display obesity, hypothermia, and lower sympathetic activity. Recombinant adeno-associated virus (rAAV)-mediated Ugcg delivery to the arcuate nucleus (Arc) significantly ameliorated obesity, specifying gangliosides as seminal components for hypothalamic regulation of body energy homeostasis. Public Library of Science 2013-03-12 /pmc/articles/PMC3595213/ /pubmed/23554574 http://dx.doi.org/10.1371/journal.pbio.1001506 Text en © 2013 Nordström et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Nordström, Viola Willershäuser, Monja Herzer, Silke Rozman, Jan von Bohlen und Halbach, Oliver Meldner, Sascha Rothermel, Ulrike Kaden, Sylvia Roth, Fabian C. Waldeck, Clemens Gretz, Norbert de Angelis, Martin Hrabě Draguhn, Andreas Klingenspor, Martin Gröne, Hermann-Josef Jennemann, Richard Neuronal Expression of Glucosylceramide Synthase in Central Nervous System Regulates Body Weight and Energy Homeostasis |
title | Neuronal Expression of Glucosylceramide Synthase in Central Nervous System Regulates Body Weight and Energy Homeostasis |
title_full | Neuronal Expression of Glucosylceramide Synthase in Central Nervous System Regulates Body Weight and Energy Homeostasis |
title_fullStr | Neuronal Expression of Glucosylceramide Synthase in Central Nervous System Regulates Body Weight and Energy Homeostasis |
title_full_unstemmed | Neuronal Expression of Glucosylceramide Synthase in Central Nervous System Regulates Body Weight and Energy Homeostasis |
title_short | Neuronal Expression of Glucosylceramide Synthase in Central Nervous System Regulates Body Weight and Energy Homeostasis |
title_sort | neuronal expression of glucosylceramide synthase in central nervous system regulates body weight and energy homeostasis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3595213/ https://www.ncbi.nlm.nih.gov/pubmed/23554574 http://dx.doi.org/10.1371/journal.pbio.1001506 |
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