Exercise, skeletal muscle metabolism and health
Mark Hargreaves
Department of
Physiology, The University of
Skeletal muscle, by
virtue of his mass and metabolic characteristics, has a major role in the
regulation of whole body carbohydrate, lipid and protein metabolism. A single exercise bout increases muscle
insulin sensitivity and plasma triglyceride clearance, effects that are partly mediated
by activation of key signalling pathways and
downstream targets, hormonal changes and substrate depletion. It has also been demonstrated that
contracting skeletal muscle releases bioactive molecules (“myokines”)
that contribute to physiological regulation during exercise and the systemic
benefits of exercise. Regular
exercise training increases the capacity for substrate storage, mobilization
and oxidation. Key metabolic
adaptations to training include increased muscle mitochondrial mass, enhanced
sensitivity to various hormones, notably insulin, and increased expression of
key enzymes and substrate transporters in skeletal muscle. Collectively, these adaptations have
positive benefits for metabolic and cardiovascular health. In recent years, we have been
particularly interested in the effects of acute and chronic exercise on
skeletal muscle GLUT4 expression. A
single bout of exercise increases skeletal muscle GLUT4 mRNA and over time this
results in increased GLUT4 protein expression. A key transcriptional regulator is myocyte enhancer factor 2 (MEF2), which is subject to
regulation by the class II histone deacetylase HDAC5 (a known transcriptional repressor) and phosphorylation.
Increased understanding of the molecular regulation of the expression of
key proteins, such as GLUT4, is important to inform the development of optimal exercise
interventions and associated therapeutic strategies to enhance health and well
being.
The original work of the
author has been supported by the Diabetes Australia Research Trust.
Key words: exercise,
skeletal muscle, mitochondria, GLUT4, MEF2, HDAC5