Changes in gene expression in responders and nonresponders to a low-intensity walking intervention.

OBJECTIVE Daily physical activity remains an effective strategy to prevent obesity and type 2 diabetes. However, the metabolic response to exercise training is variable, and the precise clinical and molecular determinants that mark the metabolic improvements remain unknown. We tested the hypothesis that clinical improvements in glucose control after low-intensity exercise in individuals with impaired glucose tolerance (IGT) are coupled to alterations in skeletal muscle gene expression. RESEARCH DESIGN AND METHODS We investigated 14 overweight individuals with IGT before and after a 4-month low-intensity unsupervised walking exercise intervention. Clinical and anthropometric measurements and glucose tolerance were determined before and after the intervention. Skeletal muscle biopsy specimens were obtained for mRNA expression analysis. RESULTS Waist circumference and work capacity during cycle ergometry were improved in individuals who achieved normal glucose tolerance (NGT) after exercise training (IGT-NGT; n = 9) but in not individuals who remained IGT (IGT-IGT; n = 5). Pretraining glycemic control was better in IGT-NGT compared with IGT-IGT. mRNA expression of mitochondrial markers and transcription factors was increased in IGT-NGT after exercise intervention and normalized to levels measured in a separate cohort of nonexercised individuals with NGT. Conversely, these markers were unaltered after exercise intervention in IGT-IGT. CONCLUSIONS Normalization of metabolic control can be achieved after low-intensity exercise in individuals with IGT. This can be tracked with increased mRNA expression of mitochondrial and metabolic genes in skeletal muscle. However, for individuals presenting with a greater derangement in glycemia, the potential for clinical and metabolic improvements after this low-intensity unsupervised exercise protocol appears to be limited.