Molecular correlates for maximal oxygen uptake and type 1 fibers.
Maximal oxygen uptake (Vo(2max)) and the amount of type 1 fibers are interrelated, but the underlying unifying molecular mechanisms are poorly understood. To explore these mechanisms, we related gene expression profiles in skeletal muscle biopsies of 43 age-matched men from published datasets with Vo(2max) and the amount of type 1 fibers and replicated some of the findings in muscle biopsies from 154 young and elderly individuals using real-time PCR. We identified 66 probe sets (genes or expressed sequence tags) positively and 83 probe sets inversely correlated with Vo(2max) and 171 probe sets positively and 217 probe sets inversely correlated with percentage of type 1 fibers in human skeletal muscle. Genes involved in oxidative phosphorylation (OXPHOS) showed high expression in individuals with high Vo(2max), whereas the opposite was not the case in individuals with low Vo(2max). Instead, genes such as AHNAK and BCL6 were associated with low Vo(2max). Also, expression of the OXPHOS genes NDUFB5 and ATP5C1 increased with exercise training and decreased with aging. In contrast, expression of AHNAK in skeletal muscle decreased with exercise training and increased with aging. Eleven genes (NDUFB4, COX5A, UQCRB, ATP5C1, ATP5G3, ETHE1, FABP3, ISCA1, MYST4, C9orf3, and PKIA) were positively correlated with both Vo(2max) and the percentage of type 1 fibers. Vo(2max) closely reflects expression of OXPHOS genes, particularly that of NDUFB5 and ATP5C1, in skeletal muscle, suggesting good muscle fitness. In contrast, a high expression of AHNAK was associated with a low Vo(2max) and poor muscle fitness.
Parikh
Hemang
H
Department of Clinical Sciences, Diabetes and Endocrinology, Lund University, University Hospital Malmö, Malmö, Sweden. hemang.parikh@med.lu.se
Nilsson
Emma
E
Ling
Charlotte
C
Poulsen
Pernille
P
Almgren
Peter
P
Nittby
Henrietta
H
Eriksson
Karl-Fredrik
KF
Vaag
Allan
A
Groop
Leif C
LC
D000328:Adult; D000367:Age Factors; D000368:Aged; D001706:Biopsy; D005080:Exercise Test; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010085:Oxidative Phosphorylation; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption; D010809:Physical Fitness; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014427:Twins
D010100:Oxygen