Effects of a novel MC4R agonist on maintenance of reduced body weight in diet‐induced obese mice. (9th January 2014)

• Record Type: Journal Article
• Authors: Skowronski, Alicja A.; Morabito, Michael V.; Mueller, Bridget R.; Lee, Samuel; Hjorth, Stephan; Lehmann, Anders; Watanabe, Kazuhisa; Zeltser, Lori M.; Ravussin, Yann; Rosenbaum, Michael; LeDuc, Charles A.; Leibel, Rudolph L.
• Is Part Of: Obesity. Volume 22:Number 5(2014:May)
• Page Start: 1287
• Page End: 1295
• Publication Date: 2014-01-09
• Subjects: Obesity -- Periodicals; 616.398005
• DOI: 10.1002/oby.20678
• Languages: English
• ISSNs: 1930-7381

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="oby20678-sec-0001" sec-type="section"> <title>Objective</title> <p>The physiology of the weight‐reduced (WR) state suggests that pharmacologic agents affecting energy homeostasis may have greater efficacy in WR individuals. Our aim was to establish a protocol that allows for evaluation of efficacy of weight maintenance agents and to assess the effectiveness of AZD2820, a novel melanocortin 4 receptor (MC4R) agonist in such a paradigm.</p> </sec> <sec id="oby20678-sec-0002" sec-type="section"> <title>Methods</title> <p>MC4R agonist was administered in stratified doses to mice who were either fed high‐fat diet <italic>ad libitum</italic> (AL) throughout the study; or stabilized at a 20% reduced body weight (BW), administered the drug for 4 weeks, and thereafter released from caloric restriction while continuing to receive the drug (WR).</p> </sec> <sec id="oby20678-sec-0003" sec-type="section"> <title>Results</title> <p>After release of WR mice to AL feeding, the high‐dose group (53.4 nmol/day) regained 12.4% less BW than their vehicle‐treated controls since the beginning of drug treatment. In WR mice, 10.8 nmol/day of the agonist was sufficient to maintain these animals at 95.1% of initial BW versus 53.4 nmol/day required to maintain the BW of AL animals (94.5%).</p> </sec> <sec id="oby20678-sec-0004" sec-type="section"> <title>Conclusions</title> <p>In the WR state, the MC4R agonist was comparably efficacious to a five‐fold higher dose in the AL state. This protocol provides a model for evaluating the mechanisms and quantitative efficacy of weight‐maintenance strategies and agents.</p> </sec> </abstract>