Regulation of lean mass, bone mass, and exercise tolerance by the central melanocortin system

Theodore P. Braun, Benjamin Orwoll, Xinxia Zhu, Peter R. Levasseur, Marek Szumowski, My Linh T Nguyen, Mary L. Bouxsein, Robert Klein, Daniel Marks

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Signaling via the type 4-melanocortin receptor (MC4R) is an important determinant of body weight in mice and humans, where loss of function mutations lead to significant obesity. Humans with mutations in the MC4R experience an increase in lean mass. However, the simultaneous accrual of fat mass in such individuals may contribute to this effect via mechanical loading. We therefore examined the relationship of fat mass and lean mass in mice lacking the type-4 melanocortin receptor (MC4RKO). We demonstrate that MC4RKO mice display increased lean body mass. Further, this is not dependent on changes in adipose mass, as MC4RKO mice possess more lean body mass than diet-induced obese (DIO) wild type mice with equivalent fat mass. To examine potential sources of the increased lean mass in MC4RKO mice, bone mass and strength were examined in MC4RKO mice. Both parameters increase with age in MC4RKO mice, which likely contributes to increases in lean body mass. We functionally characterized the increased lean mass in MC4RKO mice by examining their capacity for treadmill running. MC4R deficiency results in a decrease in exercise performance. No changes in the ratio of oxidative to glycolytic fibers were seen, however MC4RKO mice demonstrate a significantly reduced heart rate, which may underlie their impaired exercise performance. The reduced exercise capacity we report in the MC4RKO mouse has potential clinical ramifications, as efforts to control body weight in humans with melanocortin deficiency may be ineffective due to poor tolerance for physical activity.

Original languageEnglish (US)
Article numbere42183
JournalPLoS One
Volume7
Issue number7
DOIs
StatePublished - Jul 27 2012

Fingerprint

Melanocortins
Exercise Tolerance
Receptor, Melanocortin, Type 4
Bone
exercise
Fats
bones
Bone and Bones
mice
Exercise equipment
Nutrition
lean body mass
Fibers
Body Weight
lipids
Obese Mice
Mutation
receptors
body weight
Running

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Braun, T. P., Orwoll, B., Zhu, X., Levasseur, P. R., Szumowski, M., Nguyen, M. L. T., ... Marks, D. (2012). Regulation of lean mass, bone mass, and exercise tolerance by the central melanocortin system. PLoS One, 7(7), [e42183]. https://doi.org/10.1371/journal.pone.0042183

Regulation of lean mass, bone mass, and exercise tolerance by the central melanocortin system. / Braun, Theodore P.; Orwoll, Benjamin; Zhu, Xinxia; Levasseur, Peter R.; Szumowski, Marek; Nguyen, My Linh T; Bouxsein, Mary L.; Klein, Robert; Marks, Daniel.

In: PLoS One, Vol. 7, No. 7, e42183, 27.07.2012.

Research output: Contribution to journalArticle

Braun, TP, Orwoll, B, Zhu, X, Levasseur, PR, Szumowski, M, Nguyen, MLT, Bouxsein, ML, Klein, R & Marks, D 2012, 'Regulation of lean mass, bone mass, and exercise tolerance by the central melanocortin system', PLoS One, vol. 7, no. 7, e42183. https://doi.org/10.1371/journal.pone.0042183
Braun TP, Orwoll B, Zhu X, Levasseur PR, Szumowski M, Nguyen MLT et al. Regulation of lean mass, bone mass, and exercise tolerance by the central melanocortin system. PLoS One. 2012 Jul 27;7(7). e42183. https://doi.org/10.1371/journal.pone.0042183
Braun, Theodore P. ; Orwoll, Benjamin ; Zhu, Xinxia ; Levasseur, Peter R. ; Szumowski, Marek ; Nguyen, My Linh T ; Bouxsein, Mary L. ; Klein, Robert ; Marks, Daniel. / Regulation of lean mass, bone mass, and exercise tolerance by the central melanocortin system. In: PLoS One. 2012 ; Vol. 7, No. 7.
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