Chronic inhibition of GABA transaminase results in activation of thermogenesis and brown fat in the rat.
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.
Department of Pharmacology, St George's Hospital Medical School, Tooting, London, U.K.
R
R
Horton
N J
NJ
Rothwell
M J
MJ
Stock
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors*; D002001:Adipose Tissue, Brown / Q000187:drug effects*; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001833:Body Temperature Regulation / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D004983:Ethanolamines / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D004983:Ethanolamines; C020619:ethanolamine O-sulfate; D000612:4-Aminobutyrate Transaminase; D001418:Baclofen; D009638:Norepinephrine