Central and peripheral metabolic changes induced by gamma-hydroxybutyrate.

Détails

ID Serval
serval:BIB_2BB7F79F4146
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Central and peripheral metabolic changes induced by gamma-hydroxybutyrate.
Périodique
Sleep
Auteur(s)
Luca G., Vienne J., Vaucher A., Jimenez S., Tafti M.
ISSN
1550-9109 (Electronic)
ISSN-L
0161-8105
Statut éditorial
Publié
Date de publication
2015
Volume
38
Numéro
2
Pages
305-313
Langue
anglais
Résumé
STUDY OBJECTIVES: Gamma-hydroxybutyrate (GHB) was originally introduced as an anesthetic but was first abused by bodybuilders and then became a recreational or club drug.1 Sodium salt of GHB is currently used for the treatment of cataplexy in patients with narcolepsy. The mode of action and metabolism of GHB is not well understood. GHB stimulates growth hormone release in humans and induces weight loss in treated patients, suggesting an unexplored metabolic effect. In different experiments the effect of GHB administration on central (cerebral cortex) and peripheral (liver) biochemical processes involved in the metabolism of the drug, as well as the effects of the drug on metabolism, were evaluated in mice.
DESIGN: C57BL/6J, gamma-aminobutyric acid B (GABAB) knockout and obese (ob/ob) mice were acutely or chronically treated with GHB at 300 mg/kg.
MEASUREMENTS AND RESULTS: Respiratory ratio decreased under GHB treatment, independent of food intake, suggesting a shift in energy substrate from carbohydrates to lipids. GHB-treated C57BL/6J and GABAB null mice but not ob/ob mice gained less weight than matched controls. GHB dramatically increased the corticosterone level but did not affect growth hormone or prolactin. Metabolome profiling showed that an acute high dose of GHB did not increase the brain GABA level. In the brain and the liver, GHB was metabolized into succinic semialdehyde by hydroxyacid-oxoacid transhydrogenase. Chronic administration decreased glutamate, s-adenosylhomocysteine, and oxidized gluthathione, and increased omega-3 fatty acids.
CONCLUSIONS: Our findings indicate large central and peripheral metabolic changes induced by GHB with important relevance to its therapeutic use.
Mots-clé
GHB, antioxidant, brain, liver, metabolomics
Pubmed
Web of science
Création de la notice
08/03/2015 13:52
Dernière modification de la notice
03/03/2018 15:25
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