Abstract
Skeletal muscle exercise regulates several important metabolic genes in humans. We know little about the effects of environmental stress (heat) and mechanical stress (vibration) on skeletal muscle. Passive mechanical stress or systemic heat stress are often used in combination with many active exercise programs. We designed a method to deliver a vibration stress and systemic heat stress to compare the effects with active skeletal muscle contraction. Purpose: The purpose of this study is to examine whether active mechanical stress (muscle contraction), passive mechanical stress (vibration), or systemic whole body heat stress regulates key gene signatures associated with muscle metabolism, hypertrophy/atrophy, and inflammation/repair. Methods: Eleven subjects, six able-bodied and five with chronic spinal cord injury (SCI) participated in the study. The six able-bodied subjects sat in a heat stress chamber for 30 minutes. Five subjects with SCI received a single dose of limb-segment vibration or a dose of repetitive electrically induced muscle contractions. Three hours after the completion of each stress, we performed a muscle biopsy (vastus lateralis or soleus) to analyze mRNA gene expression. Results: We discovered repetitive active muscle contractions up regulated metabolic transcription factors NR4A3 (12.45 fold), PGC-1α (5.46 fold), and ABRA (5.98 fold); and repressed MSTN (0.56 fold). Heat stress repressed PGC-1α (0.74 fold change; p < 0.05); while vibration induced FOXK2 (2.36 fold change; p < 0.05). Vibration similarly caused a down regulation of MSTN (0.74 fold change; p < 0.05), but to a lesser extent than active muscle contraction. Vibration induced FOXK2 (p < 0.05) while heat stress repressed PGC-1α (0.74 fold) and ANKRD1 genes (0.51 fold; p < 0.05). Conclusion: These findings support a distinct gene regulation in response to heat stress, vibration, and muscle contractions. Understanding these responses may assist in developing regenerative rehabilitation interventions to improve muscle cell development, growth, and repair.
Highlights
Skeletal muscle is an important regulator of overall systemic health and well-being
We report the group mean ±standard error for a subset of genes previously identified to be associated with oxidative metabolism, muscle hypertrophy, and mitochondrial biogenesis
This study showed that active muscle contractions induced gene expression associated with metabolism, including a large up regulation of PGC-1α and down regulation of MSTN
Summary
Skeletal muscle is an important regulator of overall systemic health and well-being. Genes for physical activity have been highly conserved, as mobility, function, and human performance have been key components of survival. With the emergence of automated transportation methods (car, plane, train), and lifestyle altering technologies (television, computers, and cell phones), the primary regulator of human skeletal muscle, physical activity, has declined. The impact of this decline on healthy people, with less than optimal lifestyle choices, is profound and contributes to an obesity epidemic[1]. People with a central nervous system (CNS) injury, who are unable to activate their muscles completely, suffer from a host of systemic co-morbidities with a known link to reduced skeletal muscle activity, including diabetes and osteoporosis [3,4,5,6]. We compare three forms of stress including actively induced muscle contraction, passive mechanical vibration, and whole body heat stress on skeletal muscle gene regulation
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