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Nordström, V.* ; Willershäuser, M. ; Herzer, S.* ; Rozman, J. ; von Bohlen und Halbach, O.* ; Meldner, S.* ; Rothermel, U.* ; Kaden, S.* ; Roth, F. C.* ; Waldeck, C.* ; Gertz, N.* ; Hrabě de Angelis, M. ; Draguhn, A.* ; Klingenspor, M.* ; Gröne, H. J.* ; Jennemann, R.*

Neuronal expression of glucosylceramide synthase in central nervous system regulates body weight and energy homeostasis.

PLoS Biol. 11:e1001506 (2013)
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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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Publication type Article: Journal article
Document type Scientific Article
Keywords Diet-induced Obesity ; Central Leptin Resistance ; Messenger-rna Expression ; Insulin Sensitivity ; Signal Transducer ; Adipose-tissue ; Food-intake ; Ganglioside Gm3 ; Gene-expression ; Neuropeptide-y
ISSN (print) / ISBN 1544-9173
e-ISSN 1545-7885
Journal PLoS Biology
Quellenangaben Volume: 11, Issue: 3, Pages: , Article Number: e1001506 Supplement: ,
Publisher Public Library of Science (PLoS)
Reviewing status Peer reviewed