Change in CCK-8 response after diet-induced obesity and MC3/4-receptor blockade.
Little is known regarding satiety effects of systemically administered cholecystokinin (CCK-8) in propensity or resistance to dietary-induced obesity (DIO), and of its effect under conditions of melanocortin-3/4R blockade. We found that CCK-8 exerted greater satiety effects in DIO-prone but not DIO-resistant rats, and this occurred only when the rats were placed on a high-fat (HF) diet, when DIO-prone rats failed to compensate for the greater energy density of the diet. CCK-8 also suppressed intake stimulated by melanocortin-3/4R antagonist, SHU9119, but only after 24h of increased feeding. This suggests that under both of these conditions, responsiveness to CCK's satiety effect is not so much affected by a HF diet or significant increases in body weight per se, but by a failure to rapidly limit food intake to that needed only for metabolic need. Identification of an early feeding mediator that is most strongly activated by a HF diet or by an acute challenge to energy homeostasis should provide an ideal anti-obesity target adjunct to CCK-8.
Chandler
P C
PC
Department of Psychology, Behavioral Neuroscience Division, University of Alabama at Birmingham, Birmingham, AL 35294-1170, USA. pchandle@uab.edu
Wauford
P K
PK
Oswald
K D
KD
Maldonado
C R
CR
Hagan
M M
MM
D000818:Animals; D004032:Diet; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044104:Receptor, Melanocortin, Type 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D044105:Receptor, Melanocortin, Type 4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012528:Satiety Response / Q000187:drug effects*; D012844:Sincalide / Q000494:pharmacology*
D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; C103272:SHU 9119; D009074:Melanocyte-Stimulating Hormones; D012844:Sincalide