title: Effects of intermittent intraperitoneal infusion of salmon calcitonin on food intake and adiposity in obese rats.
abstract: Chronic administration of anorexigenic substances to experimental animals by injections or continuous infusion typically produces no effect or a transient reduction in daily food intake and body weight. Our aim was to identify an intermittent dosing strategy for intraperitoneal infusion of salmon calcitonin (sCT), a homolog of amylin that produces a sustained 25-35% reduction in daily food intake and adiposity in diet-induced obese rats. Rats (649 +/- 10 g body wt, 27 +/- 1% body fat), with intraperitoneal catheters tethered to infusion swivels, had free access to a 45% fat diet. Food intake, body weight, and adiposity during the 7-wk test period were relatively stable in the vehicle-treated rats (n = 16). None of 10 sCT dosing regimens administered in succession to a second group of rats (n = 18) produced a sustained 25-35% reduction in daily food intake for >5 days, although body weight and adiposity were reduced by 9% (587 +/- 12 vs. 651 +/- 14 g) and 22% (20.6 +/- 1.2 vs. 26.5 +/- 1.1%), respectively, across the 7-wk period. The declining inhibitory effect of sCT on daily food intake with the 6-h interinfusion interval appeared to be due in part to an increase in food intake between infusions. The declining inhibitory effect of sCT on daily food intake with the 2- to 3-h interinfusion interval suggested possible receptor downregulation and tolerance to frequent sCT administration; however, food intake increased dramatically when sCT was discontinued for 1 day after apparent loss of treatment efficacy. Together, these results demonstrate the activation of a potent homeostatic response to increase food intake when sCT reduces food intake and energy reserves in diet-induced obese rats.
authors.affiliation: Dept. of Veterans Affairs-Nebraska Western Iowa Health Care System, Creighton University, Omaha, NE 68105, USA.
authors.forename: Prasanth K
authors.initials: PK
authors.lastname: Chelikani
authors.forename: Alvin C
authors.initials: AC
authors.lastname: Haver
authors.forename: Roger D
authors.initials: RD
authors.lastname: Reidelberger
mesh_terms: D050154:Adiposity / Q000187:drug effects*; D000682:Amyloid / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002116:Calcitonin / Q000008:administration & dosage / Q000494:pharmacology*; D004032:Diet; D004435:Eating / Q000187:drug effects*; D007263:Infusions, Parenteral; D058228:Islet Amyloid Polypeptide; D008297:Male; D009765:Obesity / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000682:Amyloid; D058228:Islet Amyloid Polypeptide; C028815:salmon calcitonin; D002116:Calcitonin