Voluntary exercise delays monogenetic obesity and overcomes reproductive dysfunction of the melanocortin-4 receptor knockout mouse

B. G. Irani, Z. Xiang, M. C. Moore, R. J. Mandel, C. Haskell-Luevano

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


The melanocortin system is involved in hypothalamic regulation of energy homeostasis. The melanocortin-4 receptor (MC4R) has been linked to both obesity and reproductive dysfunction. Deletion of the MC4R from the mouse genome has resulted in phenotypes including adult onset obesity, hyperphagia, and difficulty in reproducing when homozygote parents are bred. Additionally, polymorphisms of the human MC4R have been identified in morbidly obese children and adults. Herein, we have identified that voluntary exercise, provided via the presence of a running wheel, impedes the monogenetic obesity (at 20 weeks of age running wheel housed body weight = 31 ± 1.8 g versus conventionally housed body weight = 41 ± 2.3 g, a 25% decrease in body weight p < 0.01), hyperphagia (average cumulative food intake is not statistically different than wild type mice housed in running wheel cages), and reproductive dysfunction phenotypes associated with the MC4R knockout mice housed by conventional means. These data demonstrate the novel finding that voluntary exercise at a young age may hinder genetically induced obesity.

Original languageEnglish (US)
Pages (from-to)638-644
Number of pages7
JournalBiochemical and Biophysical Research Communications
Issue number3
StatePublished - Jan 21 2005
Externally publishedYes

Bibliographical note

Funding Information:
We graciously acknowledge Dr. Dennis Huszar at Millennium Pharmaceuticals for providing the MC4RKO mice. This work has been supported by NIH Grant RO1-DK57080 (C.H.L.). Carrie Haskell-Luevano is a recipient of a Burroughs Wellcome fund Career Award in the Biomedical Sciences and an American Diabetes Association Research Award. Boman Irani is a recipient of an American Heart Predoctoral fellowship.

Copyright 2012 Elsevier B.V., All rights reserved.


  • AGRP
  • Agouti
  • Energy homeostasis
  • Exercise
  • Knockout mice
  • Leptin
  • MC4R
  • Melanocortin
  • Obesity
  • POMC
  • Running wheel

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