NDLI: Effects of a novel MC4R agonist on maintenance of reduced body weight in diet-induced obese mice.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	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.
Description	Country affiliation: United States Author Affiliation: Skowronski AA ( Department of Pediatrics, Division of Molecular Genetics, Columbia University, College of Physicians and Surgeons, New York, NY, USA.)
Abstract	OBJECTIVE: 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. METHODS: MC4R agonist was administered in stratified doses to mice who were either fed high-fat diet ad libitum (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). RESULTS: 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%). CONCLUSIONS: 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.
File Format	HTM / HTML
ISSN	19307381
e-ISSN	1930739X
DOI	10.1002/oby.20678
Journal	Obesity
Issue Number	5
Volume Number	22
Language	English
Publisher	Wiley-Blackwell
Publisher Date	2014-05-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Endocrinology Body Weight Drug Effects Obesity Drug Therapy Receptor, Melanocortin, Type 4 Agonists Animals Blood Glucose Metabolism Body Composition Caloric Restriction Calorimetry, Indirect Diet, High-fat Adverse Effects Energy Metabolism Hormones Blood Mice Mice, Inbred C57bl Mice, Obese Weight Loss Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Nutrition and Dietetics Endocrinology, Diabetes and Metabolism Endocrinology

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Effects of a novel MC4R agonist on maintenance of reduced body weight in diet induced obese mice

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