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Am J Physiol Endocrinol Metab 294: E1152-E1159, 2008. First published April 29, 2008; doi:10.1152/ajpendo.90255.2008
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Molecular correlates for maximal oxygen uptake and type 1 fibers

Hemang Parikh,1 Emma Nilsson,2 Charlotte Ling,1 Pernille Poulsen,2 Peter Almgren,1 Henrietta Nittby,1 Karl-Fredrik Eriksson,1 Allan Vaag,1,2 and Leif C. Groop1,3

1Department of Clinical Sciences, Diabetes and Endocrinology, Lund University, University Hospital Malmö, Malmö, Sweden; 2Steno Diabetes Center, Gentofte, Denmark; and 3Department of Medicine, Helsinki University, Helsinki, Finland

Submitted 26 February 2008 ; accepted in final form 21 April 2008

Maximal oxygen uptake (VO2max) 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 VO2max 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 VO2max 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 VO2max, whereas the opposite was not the case in individuals with low VO2max. Instead, genes such as AHNAK and BCL6 were associated with low VO2max. 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 VO2max and the percentage of type 1 fibers. VO2max 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 VO2max and poor muscle fitness.

aging; AHNAK; oxidative phosphorylation; exercise



Address for reprint requests and other correspondence: H. Parikh, Dept. of Clinical Sciences, Diabetes and Endocrinology, Lund Univ., CRC, Univ. Hospital Malmö, 20502 Malmö, Sweden (e-mail: hemang.parikh{at}med.lu.se)







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