Cited by 73Regulation of Appetite and ObesityAdipokines, Inflammation, and Metabolic DiseasesHypothalamic control of reproductive hormones

Voluntary exercise prevents the obese and diabetic metabolic syndrome of the melanocortin‐4 receptor knockout mouse

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Haskell‐Luevano, Carrie, Schaub, Jay W., Andreasen, Amy, Haskell, Kim R., Moore, Marcus C., Koerper, Lorraine M., Rouzaud, Francois, Baker, Henry V. +4 more·2009·The FASEB Journal

Abstract

Exercise is a mechanism for maintenance of body weight in humans. Morbidly obese human patients have been shown to possess single nucleotide polymorphisms in the melanocortin‐4 receptor (MC4R). MC4R knockout mice have been well characterized as a genetic model that possesses phenotypic metabolic disorders, including obesity, hyperphagia, hyperinsulinemia, and hyperleptinemia, similar to those observed in humans possessing dysfunctional hMC4Rs. Using this model, we examined the effect of voluntary exercise of MC4R knockout mice that were allowed access to a running wheel for a duration of 8 wk. Physiological parameters that were measured included body weight, body composition of fat and lean mass, food consumption, body length, and blood levels of cholesterol and nonfasted glucose, insulin, and leptin. At the termination of the experiment, hypothalamic mRNA expression levels of neuropeptide Y (NPY), agouti‐related protein (AGRP), proopiomelanocortin (POMC), cocaine‐and amphetamine‐regulated transcript (CART), orexin, brain‐derived neurotropic factor (BDNF), phosphatase with tensin homology (Pten), melanocortin‐3 receptor (MC3R), and NPY‐Y1R were determined. In addition, islet cell distribution and function in the pancreas were examined. In the exercising MC4R knockout mice, the pancreatic islet cell morphology and other physiological parameters resembled those observed in the wild‐type littermate controls. Gene expression profiles identified exercise as having a significant effect on hypothalamic POMC, orexin, and MC3R levels. Genotype had a significant effect on AGRP, POMC, CART, and NPY‐Y1R, with an exercise and genotype interaction effect on NPY gene expression. These data support the hypothesis that voluntary exercise can prevent the genetic predisposition of melanocortin‐4 receptor‐associated obesity and diabetes.—Haskell‐Luevano, C., Schaub, J. W., Andreasen, A., Haskell, K. R., Moore, M. C., Koerper, L. M., Rouzaud, F., Baker, H. V., Millard, W. J., Walter, G., Litherland, S. A., Xiang, Z. Voluntary exercise prevents the obese and diabetic metabolic syndrome of the melanocortin‐4 receptor knockout mouse. FASEB J . 23, 642–655 (2009)

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  • Obesity is primarily prevented in at least two genetically modified obese rodent models by allowing natural, instinctive voluntary running.

    “Obesity is primarily prevented in at least two genetically modified, obese rodent models by allowing natural, instinctive voluntary running.”

    From Lack of Exercise Is a Major Cause of Chronic Diseases (2012) · cites this paper as [224]

  • Mice lacking expression of the melanocortin-4 receptor exhibit maturity-onset obesity with hyperphagia, hyperinsulinemia, and hyperglycemia that is prevented by providing access to wheels for voluntary running.

    “Mice lacking expression of the melanocortin-4 receptor (MC4-R) exhibit maturity-onset obesity with hyperphagia, hyperinsulinemia, and hyperglycemia, that is prevented by providing access to wheels for voluntary running (224).”

    From Lack of Exercise Is a Major Cause of Chronic Diseases (2012) · cites this paper as [224]

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Authors
Haskell‐Luevano, C., Schaub, J. W., Andreasen, A., Haskell, K. R., Moore, M. C., Koerper, L. M., Rouzaud, F., Baker, H. V., Millard, W. J., Walter, G., Litherland, S. A., & Xiang, Z.
Affiliations
  • University of Florida Health (US)
  • Department of Pharmacodynamics, College of Pharmacy University of Florida Gainesville Florida USA
  • University of Florida (US)
Venue
The FASEB Journal
Publisher
Wiley
Published
2008-10-29
Volume
23
Issue
2
Pages
642-655
ISSN
  • 0892-6638 (ISSN-L)
  • 1530-6860
OpenAlex
W2054689428
Cited by
72
References
87
Citations by year
2026: 1 · 2022: 1 · 2021: 3 · 2020: 1 · 2019: 4 · 2018: 3 · 2017: 4 · 2016: 8 · 2015: 11 · 2014: 6 · 2013: 7 · 2012: 7
FWCI
2.37
Type
journal article
Language
en
Open access
Locations
  • The FASEB Journal (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK057080)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Keywords
voluntary exercise, melanocortin-4 receptor, obesity, diabetes mellitus, metabolic syndrome, running wheel, hypothalamic neuropeptides, proopiomelanocortin, orexin, melanocortin 3 receptor, neuropeptide Y, agouti-related protein, pancreatic islet cells, leptin, insulin, body composition
MeSH terms
Animals, Blood Glucose, Body Weight, Cholesterol, Diabetes Mellitus, Type 2, Gene Expression Regulation, Insulin, Liver, Magnetic Resonance Imaging, Obesity, Organ Size, Pancreas, Phenotype, Physical Conditioning, Animal, RNA, Messenger, Signal Transduction, Mice, Knockout, Leptin, Receptor, Melanocortin, Type 4, Mice

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