PMID- 18971258
OWN - NLM
STAT- MEDLINE
DCOM- 20090216
LR  - 20181113
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Print)
IS  - 0892-6638 (Linking)
VI  - 23
IP  - 2
DP  - 2009 Feb
TI  - Voluntary exercise prevents the obese and diabetic metabolic syndrome of the 
      melanocortin-4 receptor knockout mouse.
PG  - 642-55
LID - 10.1096/fj.08-109686 [doi]
AB  - 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.
FAU - Haskell-Luevano, Carrie
AU  - Haskell-Luevano C
AD  - Department of Pharmacodynamics, University of Florida, PO Box 100487, 
      Gainesville, FL 32610, USA. carrie@cop.ufl.edu
FAU - Schaub, Jay W
AU  - Schaub JW
FAU - Andreasen, Amy
AU  - Andreasen A
FAU - Haskell, Kim R
AU  - Haskell KR
FAU - Moore, Marcus C
AU  - Moore MC
FAU - Koerper, Lorraine M
AU  - Koerper LM
FAU - Rouzaud, Francois
AU  - Rouzaud F
FAU - Baker, Henry V
AU  - Baker HV
FAU - Millard, William J
AU  - Millard WJ
FAU - Walter, Glenn
AU  - Walter G
FAU - Litherland, S A
AU  - Litherland SA
FAU - Xiang, Zhimin
AU  - Xiang Z
LA  - eng
GR  - R01 DK057080/DK/NIDDK NIH HHS/United States
GR  - R01DK057080/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20081029
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Blood Glucose)
RN  - 0 (Insulin)
RN  - 0 (Leptin)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptor, Melanocortin, Type 4)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
MH  - Animals
MH  - Blood Glucose/metabolism
MH  - Body Weight
MH  - Cholesterol/blood
MH  - Diabetes Mellitus, Type 2/genetics/*metabolism/*prevention & control
MH  - Gene Expression Regulation
MH  - Insulin/blood
MH  - Leptin/blood
MH  - Liver/anatomy & histology/metabolism
MH  - Magnetic Resonance Imaging
MH  - Mice
MH  - Mice, Knockout
MH  - Obesity/genetics/*metabolism/*prevention & control
MH  - Organ Size
MH  - Pancreas/anatomy & histology/metabolism
MH  - Phenotype
MH  - Physical Conditioning, Animal/*physiology
MH  - RNA, Messenger/genetics
MH  - Receptor, Melanocortin, Type 4/*deficiency/genetics/metabolism
MH  - Signal Transduction
PMC - PMC2630780
EDAT- 2008/10/31 09:00
MHDA- 2009/02/17 09:00
PMCR- 2010/02/01
CRDT- 2008/10/31 09:00
PHST- 2008/10/31 09:00 [pubmed]
PHST- 2009/02/17 09:00 [medline]
PHST- 2008/10/31 09:00 [entrez]
PHST- 2010/02/01 00:00 [pmc-release]
AID - fj.08-109686 [pii]
AID - 08-109686 [pii]
AID - 10.1096/fj.08-109686 [doi]
PST - ppublish
SO  - FASEB J. 2009 Feb;23(2):642-55. doi: 10.1096/fj.08-109686. Epub 2008 Oct 29.