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1 Research Center For Genetic Medicine, Children's National Medical Center, Washington, DC, USA
2 Department of Medicine and Cell Biology, Division of Cardiology, Duke University Medical Center, Durham, NC, USA
3 Department of Exercise and Sport Science, and the Human Performance Laboratory and Diabetes/Obesity Center, East Carolina University, Greenville, NC, USA
* To whom correspondence should be addressed. E-mail: ehoffman {at}cnmcresearch.org.
Aerobic conditioned muscle shows increased oxidative metabolism or glucose relative to untrained muscle at a given absolute exercise intensity. The STRRIDE study is an aerobic exercise intervention in men and women with features of metabolic syndrome (Kraus et al, 2001), with four muscle biopsies taken during training and de-training time points. Here, we expanded a previous study (Hittel et al. 2003), and used mRNA profiling to investigate gene transcripts associated with energy and substrate metabolism in STRRIDE participants. We found coordinate regulation of key metabolic enzymes with aerobic training in metabolic syndrome (cytosolic aspartate aminotransferase [GOT1], lactate dehydrogenase B [LDHB] and pyruvate dehydrogenase alpha [PDHA1]). All were also quickly down-regulated by detraining, although the induction was not an acute response to activity. Protein and enzymatic assays were used to validate mRNA induction with aerobic training and loss with de-training (96 hrs to 2 wks) in 10 male and 10 female STRRIDE subjects. We propose that training coordinately increases the levels of GOT1, PDHA1 and LDHB, increasing glucose metabolism in muscle by liberating pyruvate for oxidative metabolism and therefore limiting lactate efflux. Serial measurement of fasting plasma lactate from 62 subjects from the same exercise group demonstrated a significant decrease of circulating lactate with training. We also found evidence for sex-specific molecular remodeling of muscle with UQCRC2, a component of mitochondrial respiratory complex III, which showed an increase after training that was specific to females. These biochemical adaptations complement existing molecular models for improved glucose tolerance with exercise intervention in pre-diabetic individuals.
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