Gene expression centroids that link with low intrinsic aerobic exercise capacity and complex disease risk.
A strong link exists between low aerobic exercise capacity and complex metabolic diseases. To probe this linkage, we utilized rat models of low and high intrinsic aerobic endurance running capacity that differ also in the risk for metabolic syndrome. We investigated in skeletal muscle gene-phenotype relationships that connect aerobic endurance capacity with metabolic disease risk factors. The study compared 12 high capacity runners (HCRs) and 12 low capacity runners (LCRs) from generation 18 of selection that differed by 615% for maximal treadmill endurance running capacity. On average, LCRs were heavier and had increased blood glucose, insulin, and triglycerides compared with HCRs. HCRs were higher for resting metabolic rate, voluntary activity, serum high density lipoproteins, muscle capillarity, and mitochondrial area. Bioinformatic analysis of skeletal muscle gene expression data revealed that many genes up-regulated in HCRs were related to oxidative energy metabolism. Seven mean mRNA expression centroids, including oxidative phosphorylation and fatty acid metabolism, correlated significantly with several exercise capacity and disease risk phenotypes. These expression-phenotype correlations, together with diminished skeletal muscle capillarity and mitochondrial area in LCR rats, support the general hypothesis that an inherited intrinsic aerobic capacity can underlie disease risks.
Kivelä
Riikka
R
Neuromuscular Research Center, Department of Biology of Physical Activity, University of Jyväskylä, Jyväskylä, Finland.
Silvennoinen
Mika
M
Lehti
Maarit
M
Rinnankoski-Tuikka
Rita
R
Purhonen
Tatja
T
Ketola
Tarmo
T
Pullinen
Katri
K
Vuento
Meri
M
Mutanen
Niina
N
Sartor
Maureen A
MA
Reunanen
Hilkka
H
Koch
Lauren G
LG
Britton
Steven L
SL
Kainulainen
Heikki
H
D000818:Animals; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000235:genetics; D017079:Exercise Tolerance / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D007150:Immunohistochemistry; D008659:Metabolic Diseases / Q000209:etiology* / Q000235:genetics; D008928:Mitochondria / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010101:Oxygen Consumption / Q000235:genetics; D010805:Physical Conditioning, Animal; D051381:Rats; D012307:Risk Factors
D018995:Myosin Heavy Chains