Document Detail

Multi-hormonal weight loss combinations in diet-induced obese rats: therapeutic potential of cholecystokinin?
MedLine Citation:
PMID:  20206194     Owner:  NLM     Status:  MEDLINE    
Cholecystokinin (CCK) acutely synergizes with amylin to suppress food intake in lean mice. To extend on these findings, the present studies sought to identify neural correlates for the interaction of amylin and CCK, as well as further understand the therapeutic potential of CCK-based combinations in obesity. First, c-Fos activation was assessed in various brain nuclei after a single intraperitoneal injection of amylin (5microg/kg) and/or CCK (5microg/kg). Amylin and CCK additively increased c-Fos within the area postrema (AP), predominantly in noradrenergic (e.g., dopamine-beta-hydroxylase-containing) cells. Next, amylin (100 or 300microg/kg/d) and/or CCK (100 or 300microg/kg/d) were subcutaneously infused for 7days in diet-induced obese (DIO) rats. Amylin treatment of DIO rats for 7days induced significant body weight loss. CCK, while ineffective alone, significantly enhanced body weight loss when co-administered with the higher dose of amylin. Finally, the addition of CCK (300microg/kg/d) to leptin (125microg/kg/d), and to the combination of amylin (50microg/kg/d) and leptin (125microg/kg/d), was also explored in DIO rats via sustained subcutaneous infusion for 14days. Infusion of amylin/leptin/CCK for 14days exerted significantly greater body weight loss, inhibition of food intake, and reduction in adiposity compared to amylin/leptin treatment alone in DIO rats. However, co-infusion of CCK and leptin was an ineffective weight loss regimen in this model. Whereas CCK agonism alone is ineffective at eliciting or maintaining weight loss, it durably augmented the food intake and body weight-lowering effects of amylin and amylin/leptin in a relevant disease model, and when combined with amylin, cooperatively activated neurons within the caudal brainstem.
James L Trevaskis; Victoria F Turek; Peter S Griffin; Carrie Wittmer; David G Parkes; Jonathan D Roth
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Publication Detail:
Type:  Journal Article     Date:  2010-03-03
Journal Detail:
Title:  Physiology & behavior     Volume:  100     ISSN:  1873-507X     ISO Abbreviation:  Physiol. Behav.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-04-05     Completed Date:  2010-06-24     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0151504     Medline TA:  Physiol Behav     Country:  United States    
Other Details:
Languages:  eng     Pagination:  187-95     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Inc. All rights reserved.
Amylin Pharmaceuticals, Inc., 9360 Towne Centre Drive, San Diego, CA 92121, United States.
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MeSH Terms
Amyloid / pharmacology,  therapeutic use
Analysis of Variance
Appetite Depressants / pharmacology,  therapeutic use
Area Postrema / drug effects,  metabolism,  pathology
Body Weight / drug effects
Cholecystokinin / therapeutic use*
Disease Models, Animal
Dopamine beta-Hydroxylase / metabolism
Dose-Response Relationship, Drug
Drug Therapy, Combination / methods
Eating / drug effects
Leptin / pharmacology,  therapeutic use
Neurons / metabolism
Obesity* / drug therapy,  etiology,  metabolism
Proto-Oncogene Proteins c-fos / metabolism
Rats, Sprague-Dawley
Weight Loss / drug effects
Reg. No./Substance:
0/Amyloid; 0/Appetite Depressants; 0/Leptin; 0/Proto-Oncogene Proteins c-fos; 106602-62-4/amylin; 9011-97-6/Cholecystokinin; EC beta-Hydroxylase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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