title: Gene expression centroids that link with low intrinsic aerobic exercise capacity and complex disease risk.
abstract: 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.
authors.affiliation: Neuromuscular Research Center, Department of Biology of Physical Activity, University of Jyväskylä, Jyväskylä, Finland.
authors.forename: Riikka
authors.initials: R
authors.lastname: Kivelä
authors.forename: Mika
authors.initials: M
authors.lastname: Silvennoinen
authors.forename: Maarit
authors.initials: M
authors.lastname: Lehti
authors.forename: Rita
authors.initials: R
authors.lastname: Rinnankoski-Tuikka
authors.forename: Tatja
authors.initials: T
authors.lastname: Purhonen
authors.forename: Tarmo
authors.initials: T
authors.lastname: Ketola
authors.forename: Katri
authors.initials: K
authors.lastname: Pullinen
authors.forename: Meri
authors.initials: M
authors.lastname: Vuento
authors.forename: Niina
authors.initials: N
authors.lastname: Mutanen
authors.forename: Maureen A
authors.initials: MA
authors.lastname: Sartor
authors.forename: Hilkka
authors.initials: H
authors.lastname: Reunanen
authors.forename: Lauren G
authors.initials: LG
authors.lastname: Koch
authors.forename: Steven L
authors.initials: SL
authors.lastname: Britton
authors.forename: Heikki
authors.initials: H
authors.lastname: Kainulainen
mesh_terms: 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
chemical_list: D018995:Myosin Heavy Chains