Voluntary Running Attenuates Metabolic Dysfunction in Ovariectomized Low-Fit Rats.
Ovariectomy and high-fat diet (HFD) worsen obesity and metabolic dysfunction associated with low aerobic fitness. Exercise training mitigates metabolic abnormalities induced by low aerobic fitness, but whether the protective effect is maintained after ovariectomy and HFD is unknown.



This study determined whether, after ovariectomy and HFD, exercise training improves metabolic function in rats bred for low intrinsic aerobic capacity.



Female rats selectively bred for low (LCR) and high (HCR) intrinsic aerobic capacity (n = 30) were ovariectomized, fed HFD, and randomized to either a sedentary (SED) or voluntary wheel running (EX) group. Resting energy expenditure, glucose tolerance, and spontaneous physical activity were determined midway through the experiment, whereas body weight, wheel running volume, and food intake were assessed throughout the study. Body composition, circulating metabolic markers, and skeletal muscle gene and protein expression were measured at sacrifice.



EX reduced body weight and adiposity in LCR rats (-10% and -50%, respectively; P < 0.05) and, unexpectedly, increased these variables in HCR rats (+7% and +37%, respectively; P < 0.05) compared with their respective SED controls, likely because of dietary overcompensation. Wheel running volume was approximately fivefold greater in HCR than LCR rats, yet EX enhanced insulin sensitivity equally in LCR and HCR rats (P < 0.05). This EX-mediated improvement in metabolic function was associated with thee gene upregulation of skeletal muscle interleukin-6 and interleukin-10. EX also increased resting energy expenditure, skeletal muscle mitochondrial content (oxidative phosphorylation complexes and citrate synthase activity), and adenosine monophosphate-activated protein kinase activation similarly in both lines (all P <0.05).



Despite a fivefold difference in running volume between rat lines, EX similarly improved systemic insulin sensitivity, resting energy expenditure, and skeletal muscle mitochondrial content and adenosine monophosphate-activated protein kinase activation in ovariectomized LCR and HCR rats fed HFD compared with their respective SED controls.
1Nutrition and Exercise Physiology, University of Missouri, Columbia, MO; 2Child Health, University of Missouri, Columbia, MO; 3Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO; 4Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, MI; 5Department of Molecular Integrative Physiology, University of Kansas Medical Center, Kansas City, KS; and 6Biomedical Sciences, University of Missouri, Columbia, MO.
Young-Min
YM
Park
Jaume
J
Padilla
Jill A
JA
Kanaley
Terese M
TM
Zidon
Rebecca J
RJ
Welly
Steven L
SL
Britton
Lauren G
LG
Koch
John P
JP
Thyfault
Frank W
FW
Booth
Victoria J
VJ
Vieira-Potter
D050154:Adiposity / Q000502:physiology; D000818:Animals; D002950:Citrate (si)-Synthase / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D005951:Glucose Tolerance Test; D024821:Metabolic Syndrome / Q000378:metabolism* / Q000628:therapy*; D008931:Mitochondria, Muscle / Q000201:enzymology; D018482:Muscle, Skeletal / Q000378:metabolism*; D010052:Ovariectomy; D010085:Oxidative Phosphorylation; D010805:Physical Conditioning, Animal; D012420:Running / Q000502:physiology*; D015431:Weight Loss / Q000502:physiology
D002950:Citrate (si)-Synthase; D017868:Cyclic AMP-Dependent Protein Kinases
Am J Physiol Regul Integr Comp Physiol. 2011 Jan;300(1):R175-82
21048074
Am J Physiol Endocrinol Metab. 2010 Jun;298(6):E1179-87
20233940
Diabetologia. 2009 Sep;52(9):1789-97
19370339
Med Sci Sports Exerc. 2008 Mar;40(3):495-502
18379212
Mediators Inflamm. 2014;2014:987017
25002755
J Appl Physiol (1985). 2012 Nov;113(10):1624-34
22995392
Am J Cardiol. 2012 Apr 1;109(7):988-93
22221951
N Engl J Med. 2008 Oct 23;359(17):1842-4
18946072
Diabetes Care. 1999 Sep;22(9):1462-70
10480510
Diabetologia. 2008 Oct;51(10):1912-9
18663427
Am J Physiol Endocrinol Metab. 2007 Jul;293(1):E31-41
17341547
Clin Chem. 2014 Jan;60(1):68-77
24379312
Am J Physiol Gastrointest Liver Physiol. 2008 Mar;294(3):G619-26
18174272
Am J Physiol Endocrinol Metab. 2016 Feb 1;310(3):E190-9
26646101
Appl Physiol Nutr Metab. 2010 Apr;35(2):151-62
20383225
J Clin Invest. 2013 Jul;123(7):2764-72
23863634
J Physiol Biochem. 2013 Jun;69(2):165-75
22941749
Physiol Behav. 2016 Oct 1;164(Pt A):383-9
27297873
Front Behav Neurosci. 2016 Apr 12;10:66
27147989
Diabetes. 2005 Jan;54(1):8-14
15616005
Endocrinology. 2009 May;150(5):2161-8
19179442
Eur J Clin Invest. 1993 Aug;23(8):466-73
8404998
Am J Physiol Endocrinol Metab. 2013 Aug 1;305(3):E429-38
23757406
J Appl Physiol (1985). 2005 Apr;98(4):1154-62
15772055
Endocrinology. 2009 Nov;150(11):4883-91
19819977
Am J Physiol Cell Physiol. 2007 Feb;292(2):C729-39
17050616
Am J Physiol Endocrinol Metab. 2012 Aug 15;303(4):E445-56
22550066
JAMA. 2009 May 20;301(19):2024-35
19454641
J Physiol. 2009 Apr 15;587(Pt 8):1805-16
19237421
Am J Cardiol. 2013 Jun 15;111(12):1805-11
23578351
N Engl J Med. 2002 Sep 5;347(10):716-25
12213942
Metabolism. 2006 Feb;55(2):217-23
16423629
Diabetes Care. 2004 Jan;27(1):83-8
14693971
Med Sci Sports Exerc. 2016 Jul;48(7):1259-69
26885638
Physiol Rev. 2008 Oct;88(4):1379-406
18923185
Am J Physiol Regul Integr Comp Physiol. 2015 Mar 15;308(6):R530-42
25608751
Nat Med. 2002 Jan;8(1):75-9
11786910
Womens Health (Lond). 2012 Mar;8(2):155-67
22375719
Science. 2005 Jan 21;307(5708):418-20
15662013
J Physiol. 2009 Jul 15;587(Pt 14):3729-39
19491243
Trends Cardiovasc Med. 2012 Feb;22(2):29-34
22867966
J Physiol. 2009 Dec 1;587(Pt 23):5559-68
19752112
Med Sci Sports Exerc. 2014 Jun;46(6):1089-97
24263979
Diabetologia. 1985 Jul;28(7):412-9
3899825