Central and peripheral metabolic changes induced by gamma-hydroxybutyrate

Area of Science:

• Biochemistry
• Pharmacology
• Metabolomics

Background:

• Gamma-hydroxybutyrate (GHB) has diverse uses, from anesthesia to narcolepsy treatment, but its metabolic pathways and effects remain unclear.
• Previous observations suggest GHB influences growth hormone release and weight loss, hinting at significant metabolic roles.

Purpose of the Study:

• To investigate the central and peripheral metabolic effects of Gamma-hydroxybutyrate (GHB) in mice.
• To elucidate the metabolic pathways and biochemical changes induced by GHB administration.

Main Methods:

• Mice (C57BL/6J, GABAB knockout, and obese ob/ob) were treated with Gamma-hydroxybutyrate (GHB) at 300 mg/kg, acutely or chronically.
• Metabolome profiling and biochemical analyses were performed on brain and liver tissues.

Main Results:

• GHB treatment decreased respiratory ratio, indicating a shift towards lipid metabolism, and reduced weight gain in most mouse models.
• GHB significantly increased corticosterone levels but did not affect growth hormone or prolactin.
• Metabolomic analysis revealed GHB is converted to succinic semialdehyde in the brain and liver; chronic use altered glutamate, s-adenosylhomocysteine, oxidized glutathione, and omega-3 fatty acids.

Conclusions:

• Gamma-hydroxybutyrate (GHB) induces substantial central and peripheral metabolic alterations.
• These findings have significant implications for understanding GHB's therapeutic applications and potential side effects.