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.
Horton
R
R
Department of Pharmacology, St George's Hospital Medical School, Tooting, London, U.K.
Rothwell
N J
NJ
Stock
M J
MJ
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