CONTEXT: Mitochondrial function is associated with aerobic physical fitness and insulin sensitivity and may play an important role in the pathophysiology of type 2 diabetes. Peroxisome proliferator-activated receptor (PPAR)-delta (gene PPARD) and PPARgamma coactivator 1alpha (gene PPARGC1A) are determinants of mitochondrial function in animals and in vitro. OBJECTIVE: The objective of this study was to establish whether single-nucleotide polymorphisms (SNPs) in PPARD and PPARGC1A modulate the effect of exercise training on change in aerobic physical fitness and insulin sensitivity and whether they affect mitochondrial function in human myotubes in vitro. SETTING: The study setting was the Tuebingen Lifestyle Intervention Program in a university teaching hospital. RESULTS: After 9 months of intervention, the minor G allele of SNP rs2267668 in PPARD and the minor serine-encoding allele of the common Gly482Ser SNP in PPARGC1A were independently associated with less increase in individual anaerobic threshold (n = 136, P = 0.002 and P = 0.005), a precise measurement of aerobic physical fitness. Moreover, individual anaerobic threshold (+11%) and insulin sensitivity (+4%) increased less in subjects carrying the minor alleles at both SNPs (X/G-X/Ser), compared with homozygous carriers of the major alleles (A/A-Gly/Gly, +120% and +40%; P < 0.0001 and P = 0.015), suggesting an additive effect of the SNPs. In addition, low skeletal muscle mitochondrial function in vitro was detected in young carriers of the G allele of the SNP rs2267668 in PPARD (n = 19, P = 0.02). CONCLUSIONS: These data provide evidence that the rs2267668 A/G SNP in PPARD and the Gly482Ser SNP in PPARGC1A have both independent and additive effects on the effectiveness of aerobic exercise training to increase aerobic physical fitness and insulin sensitivity.
CONTEXT: Mitochondrial function is associated with aerobic physical fitness and insulin sensitivity and may play an important role in the pathophysiology of type 2 diabetes. Peroxisome proliferator-activated receptor (PPAR)-delta (gene PPARD) and PPARgamma coactivator 1alpha (gene PPARGC1A) are determinants of mitochondrial function in animals and in vitro. OBJECTIVE: The objective of this study was to establish whether single-nucleotide polymorphisms (SNPs) in PPARD and PPARGC1A modulate the effect of exercise training on change in aerobic physical fitness and insulin sensitivity and whether they affect mitochondrial function in human myotubes in vitro. SETTING: The study setting was the Tuebingen Lifestyle Intervention Program in a university teaching hospital. RESULTS: After 9 months of intervention, the minor G allele of SNP rs2267668 in PPARD and the minor serine-encoding allele of the common Gly482Ser SNP in PPARGC1A were independently associated with less increase in individual anaerobic threshold (n = 136, P = 0.002 and P = 0.005), a precise measurement of aerobic physical fitness. Moreover, individual anaerobic threshold (+11%) and insulin sensitivity (+4%) increased less in subjects carrying the minor alleles at both SNPs (X/G-X/Ser), compared with homozygous carriers of the major alleles (A/A-Gly/Gly, +120% and +40%; P < 0.0001 and P = 0.015), suggesting an additive effect of the SNPs. In addition, low skeletal muscle mitochondrial function in vitro was detected in young carriers of the G allele of the SNP rs2267668 in PPARD (n = 19, P = 0.02). CONCLUSIONS: These data provide evidence that the rs2267668 A/G SNP in PPARD and the Gly482Ser SNP in PPARGC1A have both independent and additive effects on the effectiveness of aerobic exercise training to increase aerobic physical fitness and insulin sensitivity.
Authors: K Müssig; M Heni; C Thamer; K Kantartzis; F Machicao; N Stefan; A Fritsche; H-U Häring; H Staiger Journal: Diabetologia Date: 2009-11-29 Impact factor: 10.122
Authors: Kelly Claire Simon; Shirley Eberly; Xiang Gao; David Oakes; Caroline M Tanner; Ira Shoulson; Stanley Fahn; Michael A Schwarzschild; Alberto Ascherio Journal: Ann Neurol Date: 2014-10-03 Impact factor: 10.422
Authors: Sven Haufe; Stefan Engeli; Petra Budziarek; Wolfgang Utz; Jeanette Schulz-Menger; Mario Hermsdorf; Susanne Wiesner; Christoph Otto; Verena Haas; Armin de Greiff; Friedrich C Luft; Michael Boschmann; Jens Jordan Journal: Diabetes Date: 2010-03-31 Impact factor: 9.461
Authors: M Gielen; M S Westerterp-Plantenga; F G Bouwman; A M C P Joosen; R Vlietinck; C Derom; M P Zeegers; E C M Mariman; K R Westerterp Journal: Genes Nutr Date: 2014-07-05 Impact factor: 5.523