Effects of hypoxic living and training on gene expression in an obese rat model

The study's purpose was to determine in a rat obesity model the effects of normoxic training, sedentary hypoxic living, or hypoxic living plus training on the skeletal muscle messenger RNA (mRNA) levels of 14 genes involved in oxygen sensing (hypoxia-inducible factor 1α, vascular endothelial growth factor, myoglobin), glucose metabolism (glucose transporter 4, muscle phosphofructokinase), mitochondrial biogenesis (peroxisome proliferator-activated receptor γ coactivator 1-α, nuclear respiratory factor 1) and function (citrate synthase, mitochondrial-encoded cytochrome oxidase subunit 1), pH regulation (monocarboxylate transporter 1, carbonic anhydrase 3), and antioxidant defense (manganese superoxide dismutase, copper/zinc superoxide dismutase, glutathione S-transferase pi).

One hundred thirty male 3-wk-old Sprague-Dawley rats were fed a high-fat diet (4100 kcal·kg(-1)) for 3 months (all reaching a final weight >415 g) and then randomly assigned to the following groups (n = 10 per group): C (control, 2 d of sedentary living in normoxic conditions), TN1-TN4 (1-4 wk of normoxic treadmill training), SH1-SH4 (1-4 wk of sedentary hypoxic living (13.6% O2)), or TH1-TH4 (1-4 wk of hypoxic living (13.6% O2) + hypoxic treadmill training). Individual mRNA levels recorded for TN1-TN4, SH1-SH4, and TH1-TH4 were expressed relative to the mean obtained in C for each gene.

Through a two-way ANOVA, a significant interaction (treatment × treatment duration) effect was detected on expression levels of mRNAs for hypoxia-inducible factor 1α, vascular endothelial growth factor, myoglobin, nuclear respiratory factor 1, citrate synthase, carbonic anhydrase 3, monocarboxylate transporter 1, copper/zinc superoxide dismutase, glutathione S-transferase pi, and manganese superoxide dismutase. Expression levels were overall highest when training and living under hypoxia, usually after 3 wk (TH3), i.e., 79%-99% higher than the lowest values (usually corresponding to TN2) and 15.5%-53.9% higher than the second highest values (usually TH4). Normoxic training elicited no greater response than hypoxic sedentary living.

In our obese rat model, hypoxic living conditions, especially if accompanied by hypoxic exercise training, can lead to health-related molecular adaptations at the skeletal muscle level.