Exercise training increases electron and substrate shuttling proteins in muscle of overweight men and women with the metabolic syndrome

Abstract

Aerobic conditioned muscle shows increased oxidative metabolism or glucose relative to untrained muscle at a given absolute exercise intensity. The studies of a targeted risk reduction intervention through defined exercise (STRRIDE) study is an aerobic exercise intervention in men and women with features of metabolic syndrome (Kraus WE, Torgan CE, Duscha BD, Norris J, Brown SA, Cobb FR, Bales CW, Annex BH, Samsa GP, Houmard JA, and Slentz CA, Med Sci Sports Exerc 33: 1774-1784, 2001), with four muscle biopsies taken during training and detraining time points. Here, we expanded a previous study (Hittel DS, Kraus WE, and Hoffman EP, J Physiol 548: 401-410, 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 (aspartate aminotransferase 1, lactate dehydrogenase B, and pyruvate dehydrogenase-alpha(1)). All were also quickly downregulated 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 detraining (96 h to 2 wk) in 10 male and 10 female STRRIDE subjects. We propose that training coordinately increases the levels of aspartate aminotransferase 1, lactate dehydrogenase B, and pyruvate dehydrogenase-alpha(1) subunit, 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 ubiquinol-cytochrome c reductase core protein II, a component of mitochondrial respiratory complex III, which showed an increase after training that was specific to women. These biochemical adaptations complement existing molecular models for improved glucose tolerance with exercise intervention in prediabetic individuals.

Proteome Analysis of Skeletal Muscle From Obese and Morbidly Obese Women

“…Regardless of the cause, obesity is an independent risk factor for the development of cardiovascular disease, insulin resistance, and the eventual onset of type 2 diabetes (13). Skeletal muscle contributes significantly to the maintenance of systemic substrate and energy balance and, when this balance is lost, to the pathophysiology of obesityrelated diseases (2)(3)(4)(5)(6)10,11,22,23). This makes muscle an attractive target organ for the identification of diagnostic biomarkers for the onset and progression of these disease states.…”

Increased Secretion and Expression of Myostatin in Skeletal Muscle From Extremely Obese Women

“…In all, 50 g protein was collected per sample, separated by SDS-PAGE, and transferred to Immobilon-P PVDF Membrane (Millipore). For Western blot analysis of myostatin levels in muscle, nitrogen-pulverized skeletal muscle or myotubes were extracted using digitonin buffer (10 mmol/l PIPES, 0.015% digitonin, 300 mmol/l sucrose, 100 mmol/l NaCl, 3 mmol/l MgCl 2 , 5 mmol/l EDTA, and 1 mmol/l protease inhibitor [phenylmethylsulfonyl fluoride], pH 6.8) with gentle inversion at 4°C for 40 min (20). This was then centrifuged at 8,000g for 20 min to remove insoluble cellular debris.…”

Oligonucleotide microarray expression profiling: Human skeletal muscle phenotype and aerobic exercise training

“…It was then calculated that 136 genes were modulated 41.5 fold in the female subjects, while only 96 were altered by a similar magnitude in male subjects. The authors concluded that 'women exhibit a more pronounced transcriptional response to training than men' (19). What we have noticed, is that inter-subject variability is an extremely important factor, greatly influencing the outcome of array analysis (12).…”

“…In their published analysis Hittel et al (19) utilized three male subjects and three female subjects to study the impact of 9 months of aerobic training in middle-aged subjects. The array data was published in the Journal of Applied Physiology, while the raw data was available at an earlier time via their 'interactive' array website http://pepr.cnmcresearch.org.…”

“…Secondly, using correlation analysis of the gene expression changes, were the responses of the three female subjects more alike than the similarity between the male subjects? If we consider the greater number of significant genes in the female subjects (19), then this will have little to do with sexual dimorphism and more to do with variation between subjects. Other findings included the well established changes in mitochondrial gene and protein expression.…”