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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:...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
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.
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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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