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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2013
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oai:doaj.org-article:6df52cc8e3e74af38026d85d326f29192021-11-18T05:37:13ZNeuronal expression of glucosylceramide synthase in central nervous system regulates body weight and energy homeostasis.1544-91731545-788510.1371/journal.pbio.1001506https://doaj.org/article/6df52cc8e3e74af38026d85d326f29192013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23554574/?tool=EBIhttps://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885Hypothalamic 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.Viola NordströmMonja WillershäuserSilke HerzerJan RozmanOliver von Bohlen Und HalbachOliver von Bohlen Und HalbachSascha MeldnerUlrike RothermelSylvia KadenFabian C RothClemens WaldeckNorbert GretzMartin Hrabě de AngelisAndreas DraguhnMartin KlingensporHermann-Josef GröneRichard JennemannPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 11, Iss 3, p e1001506 (2013) |
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DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Biology (General) QH301-705.5 |
| spellingShingle |
Biology (General) QH301-705.5 Viola Nordström Monja Willershäuser Silke Herzer Jan Rozman Oliver von Bohlen Und Halbach Oliver von Bohlen Und Halbach Sascha Meldner Ulrike Rothermel Sylvia Kaden Fabian C Roth Clemens Waldeck Norbert Gretz Martin Hrabě de Angelis Andreas Draguhn Martin Klingenspor Hermann-Josef Gröne Richard Jennemann Neuronal expression of glucosylceramide synthase in central nervous system regulates body weight and energy homeostasis. |
| 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 |
article |
| author |
Viola Nordström Monja Willershäuser Silke Herzer Jan Rozman Oliver von Bohlen Und Halbach Oliver von Bohlen Und Halbach Sascha Meldner Ulrike Rothermel Sylvia Kaden Fabian C Roth Clemens Waldeck Norbert Gretz Martin Hrabě de Angelis Andreas Draguhn Martin Klingenspor Hermann-Josef Gröne Richard Jennemann |
| author_facet |
Viola Nordström Monja Willershäuser Silke Herzer Jan Rozman Oliver von Bohlen Und Halbach Oliver von Bohlen Und Halbach Sascha Meldner Ulrike Rothermel Sylvia Kaden Fabian C Roth Clemens Waldeck Norbert Gretz Martin Hrabě de Angelis Andreas Draguhn Martin Klingenspor Hermann-Josef Gröne Richard Jennemann |
| author_sort |
Viola Nordström |
| title |
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_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_sort |
neuronal expression of glucosylceramide synthase in central nervous system regulates body weight and energy homeostasis. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/6df52cc8e3e74af38026d85d326f2919 |
| work_keys_str_mv |
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