Skeletal muscle mitochondrial and metabolic responses to a high-fat diet in female rats bred for high and low aerobic capacity.
Rats selected artificially to be low-capacity runners (LCR) possess a metabolic syndrome phenotype that is worsened by a high-fat diet (HFD), whereas rats selected to be high-capacity runners (HCR) are protected against HFD-induced obesity and insulin resistance. This study examined whether protection against, or susceptibility to, HFD-induced insulin resistance in the HCR-LCR strains is associated with contrasting metabolic adaptations in skeletal muscle. HCR and LCR rats (generation 20; n = 5-6; maximum running distance approximately 1800 m vs. approximately 350 m, respectively (p < 0.0001)) were divided into HFD (71.6% energy from fat) or normal chow (NC) (16.7% energy from fat) groups for 7 weeks (from 24 to 31 weeks of age). Skeletal muscle (red gastrocnemius) mitochondrial-fatty acid oxidation (FAO), mitochondrial-enzyme activity, mitochondrial-morphology, peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha), and peroxisome proliferator-activated receptor delta (PPARdelta) expression and insulin sensitivity (intraperitoneal glucose tolerance tests) were measured. The HFD caused increased adiposity and reduced insulin sensitivity only in the LCR and not the HCR strain. Isolated mitochondria from the HCR skeletal muscle displayed a 2-fold-higher rate of FAO on NC, but both groups increased FAO following HFD. PGC-1alpha mRNA expression and superoxide dismutase activity were significantly reduced with the HFD in the LCR rats, but not in the HCR rats. PPARdelta expression did not differ between strains or dietary conditions. These results do not provide a clear connection between protection of insulin sensitivity and HFD-induced adaptive changes in mitochondrial function or transcriptional responses but do not dismiss the possibility that elevated mitochondrial FAO in the HCR may play a protective role.
Naples
Scott P
SP
Department of Biomedical Sciences, University of Missouri, Columbia, MO 65211, USA.
Borengasser
Sarah J
SJ
Rector
R Scott
RS
Uptergrove
Grace M
GM
Morris
E Matthew
EM
Mikus
Catherine R
CR
Koch
Lauren G
LG
Britton
Steve L
SL
Ibdah
Jamal A
JA
Thyfault
John P
JP
D000222:Adaptation, Physiological; D050154:Adiposity; D000375:Aging / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage / Q000378:metabolism*; D004435:Eating; D004734:Energy Metabolism / Q000235:genetics; D017079:Exercise Tolerance / Q000235:genetics; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics; D008931:Mitochondria, Muscle / Q000378:metabolism* / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000648:ultrastructure; D010084:Oxidation-Reduction; D047494:PPAR delta / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics
D001786:Blood Glucose; D004041:Dietary Fats; D005227:Fatty Acids; D007328:Insulin; D047494:PPAR delta; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D013482:Superoxide Dismutase
Med Sci Sports Exerc. 1999 Jul;31(7):987-97
10416560
Am J Physiol Cell Physiol. 2007 Feb;292(2):C729-39
17050616
Am J Physiol Endocrinol Metab. 2007 Jul;293(1):E31-41
17341547
J Appl Physiol (1985). 1997 Jul;83(1):166-71
9216960
Nat Genet. 2003 Jul;34(3):267-73
12808457
Diabetes. 2005 Jan;54(1):8-14
15616005
Diabetologia. 2009 Apr;52(4):574-82
19183935
J Clin Invest. 2006 Mar;116(3):590-7
16511591
Annu Rev Biochem. 2006;75:367-401
16756496
Cell Metab. 2005 Jun;1(6):361-70
16054085
Am J Physiol Gastrointest Liver Physiol. 2008 Mar;294(3):G619-26
18174272
Diabetes. 2001 Jun;50(6):1389-96
11375340
Gastroenterology. 2005 May;128(5):1381-90
15887119
Exp Gerontol. 2008 Jan;43(1):24-33
17997255
Am J Physiol Endocrinol Metab. 2008 Sep;295(3):E586-94
18577694
Diabetes. 2007 Aug;56(8):2142-7
17536063
Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8466-71
12832613
J Biol Chem. 2007 May 25;282(21):15439-50
17416903
PLoS One. 2009;4(4):e5186
19365547
FEBS Lett. 2008 Jan 9;582(1):46-53
18036349
Proc Natl Acad Sci U S A. 2003 Sep 2;100(18):10207-12
12920182
Am J Physiol Endocrinol Metab. 2007 Jun;292(6):E1782-9
17311893
J Physiol. 2009 Apr 15;587(Pt 8):1805-16
19237421
Am J Physiol. 1999 Dec;277(6):E1130-41
10600804
J Biol Chem. 2003 Jul 18;278(29):26597-603
12734177
J Biol Chem. 2002 Jul 19;277(29):26089-97
12118038
Proc Natl Acad Sci U S A. 2008 Jun 3;105(22):7815-20
18509063
Cell Metab. 2008 Jan;7(1):45-56
18177724
Physiol Genomics. 2001 Feb 07;5(1):45-52
11161005
Am J Physiol Endocrinol Metab. 2004 Dec;287(6):E1076-81
15280153
Int J Obes (Lond). 2007 Aug;31(8):1302-10
17310221
N Engl J Med. 2004 Feb 12;350(7):664-71
14960743
Obes Res. 2003 Dec;11(12):1471-9
14694211
J Biol Chem. 2004 Jun 25;279(26):27177-86
15105415
Obesity (Silver Spring). 2008 Apr;16(4):819-26
18239587
Am J Physiol Endocrinol Metab. 2003 Apr;284(4):E741-7
12626325
Am J Physiol Endocrinol Metab. 2009 Apr;296(4):E738-47
19141681
Diabetes. 2009 Mar;58(3):550-8
19073774
J Appl Physiol (1985). 2009 Jan;106(1):161-8
18974364
Cell Metab. 2005 Oct;2(4):251-61
16213227
Am J Physiol Endocrinol Metab. 2000 Nov;279(5):E1039-44
11052958
J Clin Invest. 2009 Mar;119(3):573-81
19188683
Diabetes. 2005 Jul;54(7):1926-33
15983191
J Biol Chem. 2005 Sep 30;280(39):33588-98
16079133
Science. 2005 Jan 21;307(5708):418-20
15662013
Diabetes. 2007 Aug;56(8):2085-92
17519422