Effect of intraperitoneal CCK-8 on food intake and brain orexin-A after 48 h of fasting in the rat.
We investigated the interactions of the peripheral satiety peptide cholecystokinin and the brain orexin-A system in the control of food intake. The effect of an intraperitoneal (i.p.) injection of sulfated cholecystokinin octapeptide (in this article called CCK) (5 microg/kg, 4.4 nmol/kg) or of phosphate-buffered saline (PBS, vehicle control) on 48 h fasting-induced feeding and on orexin-A peptide content was analyzed in diverse brain regions innervated by orexin neurons and involved in the control of food intake. Administration of CCK after a 48 h fast reduced fasting-induced hyperphagia (P<0.05). I.p. CCK increased the orexin-A content in the posterior brainstem of 48 h fasted rats by 35% (P<0.05). Fed animals receiving CCK had 48% higher orexin-A levels in the posterior brainstem than fasted rats (P<0.05). In the lateral hypothalamus, fasting decreased orexin-A levels by 50% as compared to fed rats (P<0.05). In the septal nuclei, the combination of fasting and CCK administration reduced orexin-A contents compared to fed PBS and CCK animals by 13% and 17%, respectively (P<0.05). These results suggest a convergence of pathways activated by peripheral CCK and by fasting on the level of orexin-A released in the posterior brainstem and provide evidence for a novel interaction between peripheral satiety signaling and a brain orexigen in the control of food intake.
Gallmann
Eva
E
Physiology and Animal Husbandry, Institute of Animal Sciences Swiss Federal Institute of Technology, Schwerzenbach, Switzerland. gallmann@ohsu.edu
Arsenijevic
Denis
D
Williams
Gareth
G
Langhans
Wolfgang
W
Spengler
Marianne
M
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D005215:Fasting / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D009479:Neuropeptides / Q000378:metabolism*; D000068797:Orexins; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D012844:Sincalide / Q000378:metabolism / Q000494:pharmacology*; D013997:Time Factors
D001786:Blood Glucose; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D012844:Sincalide