Twin Resemblance in Muscle HIF-1α Responses to Hypoxia and Exercise.
Hypoxia-inducible factor-1 (HIF-1) is a master regulator of myocellular adaptation to exercise and hypoxia. However, the role of genetic factors in regulation of HIF-1 responses to exercise and hypoxia is unknown. We hypothesized that hypoxia at rest and during exercise stimulates the HIF-1 pathway and its downstream targets in energy metabolism regulation in a genotype-dependent manner. Eleven monozygotic twin (MZ) pairs performed an experimental trial in both normoxia and hypoxia (FiO210.7%). Biopsies were taken from m. vastus lateralis before and after a 20-min submaximal cycling bout @~30% of sea-level VO2max. Key-markers of the HIF-1 pathway and glycolytic and oxidative metabolism were analyzed using real-time PCR and Western Blot. Hypoxia increased HIF-1α protein expression by ~120% at rest vs. +150% during exercise (p< 0.05). Furthermore, hypoxia but not exercise increased muscle mRNA content of HIF-1α (+50%), PHD2 (+45%), pVHL (+45%;p< 0.05), PDK4 (+1200%), as well as PFK-M (+20%) and PPAR-γ1 (+60%;p< 0.05). Neither hypoxia nor exercise altered PHD1, LDH-A, PDH-A1, COX-4, and CS mRNA expressions. The hypoxic, but not normoxic exercise-induced increment of muscle HIF-1α mRNA content was about 10-fold more similar within MZ twins than between the twins (p< 0.05). Furthermore, in resting muscle the hypoxia-induced increments of muscle HIF-1α protein content, and HIF-1α and PDK4 mRNA content were about 3-4-fold more homogeneous within than between the twins pairs (p< 0.05). The present observations in monozygotic twins for the first time clearly indicate that the HIF-1α protein as well as mRNA responses to submaximal exercise in acute hypoxia are at least partly regulated by genetic factors.
Exercise Physiology Research Group, Department of Kinesiology, KU Leuven Leuven, Belgium.
Ruud
R
Van Thienen
Exercise Physiology Research Group, Department of Kinesiology, KU Leuven Leuven, Belgium.
Evi
E
Masschelein
Exercise Physiology Research Group, Department of Kinesiology, KU Leuven Leuven, Belgium.
Gommaar
G
D'Hulst
Physical Activity, Sports and Health Research Group, Department of Kinesiology, KU Leuven Leuven, Belgium.
Martine
M
Thomis
Exercise Physiology Research Group, Department of Kinesiology, KU Leuven Leuven, Belgium.
Peter
P
Hespel
HIF-1; exercise; hypoxia; monozygotic twin design; muscle biopsies