RESUMEN
Insulin resistance (IR) is a risk factor for the development of several major metabolic diseases. Muscle fiber composition is established early in life and is associated with insulin sensitivity. Hence, muscle fiber composition was used to identify early defects in the development of IR in healthy young individuals in the absence of clinical manifestations. Biopsies were obtained from the thigh muscle, followed by an intravenous glucose tolerance test. Indices of insulin action were calculated and cardiovascular measurements, analyses of blood and muscle were performed. Whole-body insulin sensitivity (SIgalvin) was positively related to expression of type I muscle fibers (r=0.49; P<0.001) and negatively related to resting heart rate (HR, r=-0.39; P<0.001), which was also negatively related to expression of type I muscle fibers (r=-0.41; P<0.001). Muscle protein expression of endothelial nitric oxide synthase (eNOS), whose activation results in vasodilation, was measured in two subsets of subjects expressing a high percentage of type I fibers (59±6%; HR = 57±9 beats/min; SIgalvin = 1.8±0.7 units) or low percentage of type I fibers (30±6%; HR = 71±11; SIgalvin = 0.8±0.3 units; P<0.001 for all variables vs. first group). eNOS expression was: 1. higher in subjects with high type I expression; 2. almost two-fold higher in pools of type I vs. II fibers; 3. only detected in capillaries surrounding muscle fibers; and 4. linearly associated with SIgalvin. These data demonstrate that an altered function of the autonomic nervous system and a compromised capacity for vasodilation in the microvasculature occur early in the development of IR.
RESUMEN
Human skeletal muscle characteristics such as fiber type composition, fiber size, and myonuclear content are widely studied in clinical and sports-related contexts. Being aware of the methodological and biological variability of the characteristics is a critical aspect in study design and outcome interpretation, but comprehensive data on the variability of morphological features in human skeletal muscle are currently limited. Accordingly, in the present study, m. vastus lateralis biopsies (10 per subject) from young and healthy individuals, collected in a systematic manner, were analyzed for various characteristics using immunohistochemistry (n = 7) and SDS-PAGE (n = 25). None of the analyzed parameters, fiber type % (FT%), type I and II fiber cross-sectional area (fCSA), percentage fiber type area (fCSA%), myosin heavy chain composition (MyHC%), type IIX content, myonuclear content, or myonuclear domain, varied in a systematic manner longitudinally along the muscle or between the two legs. The average within-subject coefficient of variation for FT%, fCSA, fCSA%, and MyHC% ranged between 13% and 18% but was only 5% for fiber-specific myonuclear content, which reduced the variability for myonuclear domain size to 11%-12%. Pure type IIX fibers and type IIX MyHC were randomly distributed and present in <24% of the analyzed samples, with the average content being 0.1% and 1.1%, respectively. In conclusion, leg or longitudinal orientation does not seem to be an important aspect to consider when investigating human vastus lateralis characteristics. However, single muscle biopsies should preferably not be used when studying fiber type- and fiber size-related aspects, given the notable sample-to-sample variability.NEW & NOTEWORTHY This study provides a comprehensive analysis of the variability of key human skeletal muscle fiber characteristics in multiple sites along and between the m. vastus lateralis of healthy and active individuals. We found a notable but nonsystematic variability in fiber type and size, whereas myonuclear content was distinctively less variable, and the prevalence of type IIX fibers was random and very low. These data are important to consider when designing and interpreting studies including m. vastus lateralis biopsies.
