Mercaptoacetate fails to block the feeding-inhibitory effect of the beta3-adrenergic receptor agonist CGP 12177A.
Peripherally administered beta3-adrenergic receptor (beta3-AR) agonists stimulate lipolysis and inhibit food intake. To test the hypothesis that this inhibition of feeding is due to a substrate-driven increase in hepatic fatty acid oxidation (FAO), we assessed the ability of the FAO inhibitor mercaptoacetate (MA) to reverse the feeding-inhibitory effect of the beta3-AR agonist CGP 12177A (CGP). Adult male Sprague-Dawley rats received intraperitoneal injections of 1 mg/kg CGP, of 45.6 mg/kg MA, or of both drugs, and the effects on food intake, plasma free fatty acids (FFA), and plasma beta-hydroxybutyrate (BHB), an indicator for hepatic FAO, were assessed. Control rats received saline injections. CGP significantly reduced food intake after 0.5 and 6 h and increased plasma FFA and BHB at 0.5 h, suggesting increased lipolysis and hepatic FAO. MA completely reversed the increase in plasma BHB and thus appeared to effectively abolish CGP's effect on hepatic FAO, but MA failed to affect CGP's feeding-inhibitory action. These findings do not support the hypothesis that the beta3-AR agonist CGP inhibits feeding by enhancing hepatic FAO or ketogenesis. Although the beta3-AR agonist CGP reduced saccharin intake in a one-bottle condition taste aversion test, it seems unlikely that the hypophagic effect of CGP is elicited by malaise.
Brandt
Karsten
K
Institute of Animal Sciences, ETH Zurich, Schorenstrasse 16, 8603 Schwerzenbach, Switzerland.
Geary
Nori
N
Langhans
Wolfgang
W
Leonhardt
Monika
M
D020155:3-Hydroxybutyric Acid / Q000097:blood; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage*; D000704:Analysis of Variance; D000818:Animals; D001069:Appetite Regulation / Q000187:drug effects* / Q000502:physiology; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D004347:Drug Interactions; D004435:Eating / Q000187:drug effects*; D005227:Fatty Acids / Q000097:blood*; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology; D007328:Insulin / Q000097:blood; D007657:Ketone Bodies / Q000378:metabolism; D008066:Lipolysis / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010084:Oxidation-Reduction / Q000187:drug effects; D011412:Propanolamines / Q000008:administration & dosage*; D051381:Rats; D022702:Receptors, Adrenergic, beta-3 / Q000187:drug effects / Q000502:physiology; D018709:Statistics, Nonparametric; D013649:Taste; D013864:Thioglycolates / Q000008:administration & dosage*
D000318:Adrenergic beta-Agonists; D005227:Fatty Acids; D007328:Insulin; D007657:Ketone Bodies; D011412:Propanolamines; D022702:Receptors, Adrenergic, beta-3; D013864:Thioglycolates; C017487:2-mercaptoacetate; C033394:CGP 12177; D020155:3-Hydroxybutyric Acid