Chronic inhibition of GABA transaminase results in activation of thermogenesis and brown fat in the rat

Gen Pharmacol. 1988;19(3):403-5. doi: 10.1016/0306-3623(88)90037-7.

Abstract

1. Oral administration of the GABA transaminase inhibitor ethanolamine-O-sulphate (EOS, 5 mg/ml in drinking water) to rats for 14 days suppressed food intake by 24%, but reduced weight gain by over 35%. 2. Thus, feed efficiency (g gain/MJ eaten) was decreased by over 15% in EOS-treated rats, suggesting that there had been an increase in metabolic rate. 3. The thermogenic response (rise in oxygen consumption, VO2) to injection of noradrenaline was enhanced by 50% and the thermogenic activity of brown adipose tissue (BAT, assessed from mitochondrial GDP-binding) was increased by 38% in EOS-treated rats. 4. Injection of baclofen (a GABAB agonist, 0.5 mg/kg s.c.) stimulated VO2 in both groups, with a significantly greater response in EOS treated rats, and this was enhanced by bicuculline (GABAA antagonist, 0.5 g/kg s.c.) in control rats and attenuated by muscimol (GABAA agonist, 0.5 mg/kg s.c.) in control and EOS-treated rats. 5. The data indicate that increasing brain GABA concentrations with EOS results in lower levels of metabolic efficiency and increases in thermogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Aminobutyrate Transaminase / antagonists & inhibitors*
  • Adipose Tissue, Brown / drug effects*
  • Animals
  • Baclofen / pharmacology
  • Body Temperature Regulation / drug effects*
  • Body Weight / drug effects
  • Ethanolamines / pharmacology*
  • Male
  • Norepinephrine / pharmacology
  • Oxygen Consumption / drug effects
  • Rats
  • Rats, Inbred Strains

Substances

  • Ethanolamines
  • ethanolamine O-sulfate
  • 4-Aminobutyrate Transaminase
  • Baclofen
  • Norepinephrine