Neuronal expression of glucosylceramide synthase in central nervous system regulates body weight and energy homeostasis.
PLoS Biol
; 11(3): e1001506, 2013.
Article
em En
| MEDLINE
| ID: mdl-23554574
ABSTRACT
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-glucoseceramide 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-glucoseceramide 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peso Corporal
/
Sistema Nervoso Central
/
Glucosiltransferases
/
Neurônios
Limite:
Animals
Idioma:
En
Revista:
PLoS Biol
Assunto da revista:
BIOLOGIA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Alemanha