Regulatory mechanisms in skeletal muscle lipid hydrolysis. The regulation of intramuscular triglyceride (fat) utilisation by human skeletal muscle is largely unknown. Our contention is that the specialized protein enzyme, hormone sensitive lipase (HSL), has a fundamental role in intramuscular triacylglycerol utilisation and is regulated by both intramuscular levels of key metabolites and circulating hormone concentrations. We also propose control points subsequent to HSL activation are important ....Regulatory mechanisms in skeletal muscle lipid hydrolysis. The regulation of intramuscular triglyceride (fat) utilisation by human skeletal muscle is largely unknown. Our contention is that the specialized protein enzyme, hormone sensitive lipase (HSL), has a fundamental role in intramuscular triacylglycerol utilisation and is regulated by both intramuscular levels of key metabolites and circulating hormone concentrations. We also propose control points subsequent to HSL activation are important for triglyceride hydrolysis. Our proposed project examines these factors and will enhance our understanding of the regulation of muscle fat use, thereby leading to potential metabolic strategies (nutritional, pharmacological) that enhance skeletal muscle function at rest and during exercise.Read moreRead less
Reducing the fat burden: Identification of novel cellular and molecular targets for alleviating skeletal muscle insulin resistance. Insulin resistance and the associated consequences are a major public health problem in Australia and cost the healthcare system >$1.1 billion/year. Exercise training and thiaziolidinedione (TZD) treatment are therapies that partially ameliorate insulin resistance through distinct and independent mechanisms. However, neither intervention represents a viable long-ter ....Reducing the fat burden: Identification of novel cellular and molecular targets for alleviating skeletal muscle insulin resistance. Insulin resistance and the associated consequences are a major public health problem in Australia and cost the healthcare system >$1.1 billion/year. Exercise training and thiaziolidinedione (TZD) treatment are therapies that partially ameliorate insulin resistance through distinct and independent mechanisms. However, neither intervention represents a viable long-term strategy: exercise training has low compliance, while chronic TZD use is associated with several adverse side effects (edema, weight gain etc.). We will investigate the metabolic, cellular and molecular mechanisms by which these therapies each exert their positive effect on insulin action with the aim of identifying novel targets for future drug interventions. Read moreRead less
Intracellular localisation of insulin signalling proteins in human skeletal muscle following exercise. The metabolic action of insulin in skeletal muscle is enhanced by exercise, but the underlying mechanisms mediating this are unknown. Insulin receptor substrate proteins are key mediators in the intracellular insulin signalling pathway and play a central role in regulating many metabolic events. Our aim is to examine the hypothesis that exercise induces a novel subcellular redistribution of the ....Intracellular localisation of insulin signalling proteins in human skeletal muscle following exercise. The metabolic action of insulin in skeletal muscle is enhanced by exercise, but the underlying mechanisms mediating this are unknown. Insulin receptor substrate proteins are key mediators in the intracellular insulin signalling pathway and play a central role in regulating many metabolic events. Our aim is to examine the hypothesis that exercise induces a novel subcellular redistribution of these insulin receptor substrate proteins in skeletal muscle, such that the metabolic action of insulin is enhanced. Elucidating the mechanisms whereby exercise enhances insulin action underpins the development of new treatments and therapies with the aim of improving skeletal muscle function in health and disease.Read moreRead less
Molecular networks underlying mitochondrial biogenesis in humans. Mitochondria are essential for life, and we propose a highly-innovative approach (employing multiple, cutting-edge ‘omic’ technologies and bioinformatics) to advance the fundamental understanding of how mitochondria respond and adapt to exercise in humans. The project outcomes should include significant new knowledge and advanced expertise that can be used by others to facilitate additional research outcomes. The project anticipa ....Molecular networks underlying mitochondrial biogenesis in humans. Mitochondria are essential for life, and we propose a highly-innovative approach (employing multiple, cutting-edge ‘omic’ technologies and bioinformatics) to advance the fundamental understanding of how mitochondria respond and adapt to exercise in humans. The project outcomes should include significant new knowledge and advanced expertise that can be used by others to facilitate additional research outcomes. The project anticipates the contribution of innovative tools for molecular biology research, benefiting therapeutic and biotechnology applications. This project will support advanced training of young researchers in frontier technologies, which will expand Australian research capabilities and help produce a higher quality workforce.Read moreRead less