Enhanced Glucose Metabolism Is Preserved in Cultured Primary Myotubes From Obese Donors in Response to Exercise Training

Abstract

Aerobic exercise training is associated with metabolic adaptations in vivo that are preserved in human cultured primary myotubes. It can be hypothesized that skeletal muscle microenvironmental changes induced by endurance training lead to metabolic imprinting on myogenic progenitor cells.

Myotubes from lean and severely obese subjects with and without type 2 diabetes respond differently to an in vitro model of exercise

“…Lack of EPSinduced increase in insulin sensitivity in myotubes from lean nondiabetic subjects could also be explained by maximal responsiveness to insulin in those cells per se and limited capacity to respond further. In agreement with other studies reporting enhanced carbohydrate oxidation after exercise in obese subjects (9) and in subjects with T2D (50), we showed an increase in glucose oxidation after EPS in myotubes from all three donor groups. In contrast, we have previously (36) and in the present study shown that mitochondrial content was increased after EPS in myotubes from lean nondiabetic subjects, and this was followed by increased rate of oleic acid oxidation.…”

Resistance to the Beneficial Effects of Exercise in Type 2 Diabetes: Are Some Individuals Programmed to Fail?

“…Work by Nikolic et al (67) demonstrated that chronic low-frequency electrical pulse stimulation was sufficient to induce a more oxidative phenotype in lean myotubes (and hence mimic an exercise contraction)-which is consistent with our previous findings that demonstrated an improved insulin responsiveness and lipid metabolism after a pharmacological exercise mimetic in lean human myotubes (68). A recent investigation by Bourlier et al (69) demonstrated for the first time that chronic exercise in vivo was sufficient to remodel glucose metabolism in human myotubes, such that the improvements after exercise observed in vivo were retained in vitro. Taken together, these findings give further credibility to the use of human primary myotubes as a model of the in vivo phenotype.…”

Greater Oxidative Capacity in Primary Myotubes from Endurance-trained Women

“…However, we show that primary muscle cells isolated from exercise-trained skeletal muscle and grown in vitro maintain greater oxidative capacity compared to untrained donors cells. Our findings are in line with previous observations demonstrating that some exercise adaptations persist in primary myotubes grown in vitro (6,7). Together, these data suggest that primary myotubes isolated from exercise-trained individuals maintain the “exercise metabolic program” for enhanced oxidative metabolism ex vivo .…”

“…In one study, exercise-induced alterations in skeletal muscle mitochondrial content persisted in myotubes, but they did not perform functional assays to assess oxidative capacity (7). In another study, exercise training enhanced capacity for myotubes to oxidize some but not all substrates, but their exercise training protocol did not promote a robust increase in mitochondrial biogenesis in muscle biopsy samples (6). Thus, it is unclear whether human primary myotubes are valid models to study exercise-induced skeletal muscle mitochondrial adaptations.…”