Research Topic

Untangling Energy Metabolism in Skeletal Muscle: From Physiology to Pharmacology

About this Research Topic

Skeletal muscles can collectively be regarded as the largest organ in human body. Indeed, there are over 600 skeletal muscles, which under physiological conditions represent ~40% of body weight and ~20% of the resting metabolic rate. Skeletal muscles are a major organ for the conversion of lipids and glucose. At rest 70% of the energy consumption of muscle comes from fatty acids. Moreover, skeletal muscles are quantitatively the most important site of the postprandial insulin-stimulated glucose disposal and contain the largest body stores of glycogen, proteins, as well as potassium. In addition, they are not only the largest, but also one of the most dynamic metabolic organs, which undergoes a tremendous increase in metabolic rate, glucose uptake, and transmembrane ion transport between the resting and the actively contracting state.

Importantly, while the metabolic pathways in skeletal muscles are regulated by a plethora of factors, including metabolic hormones, contractions, reactive oxygen species, hypoxia, and NO, skeletal muscles do not just passively respond to regulatory signals. In fact, skeletal muscles are a major source of signal molecules (myokines) that participate in inter-organ crosstalk and actively modulate energy metabolism in other organs.

Given the size of skeletal muscles and a wide spectrum of metabolic functions performed by them it is not surprising that metabolic dysfunction of skeletal muscles, such as insulin resistance, disrupts systemic metabolic homeostasis. Furthermore, skeletal muscles are key players underpinning the well-established effects that regular exercise training has in human health and in the prevention or treatment of major, if not all, degenerative diseases, such as sarcopenia as well as neurodegenerative disorders, which are known to be associated with metabolic dysfunction. Pharmacological modulation of energy metabolism in skeletal muscle is therefore a promising strategy to combat chronic non-communicable diseases.

Clearly, the quest to untangle energy metabolism in skeletal muscles will not only broaden the boundaries of our understanding of physiology, but will have important practical ramifications, including development of new pharmacotherapies.

The aim of this Research Topic is to highlight recent developments in our understanding of energy metabolism in skeletal muscle under physiological and pathophysiological conditions and to facilitate the use of this knowledge on the road to the discovery of pharmacological targets and new pharmacotherapies. Different types of manuscripts, including original research, methodological studies, as well as reviews, will be considered.

The suggested topics include, but are not limited to:
• Regulation of metabolic pathways in skeletal muscle, including intracellular signalling.
• Skeletal muscle as a target and source of signal molecules, including metabolic hormones and myokines, which regulate energy metabolism and participate in cross-talk between skeletal muscles and other organs.
• Experimental models, including cell cultures and isolated organs, for investigation of skeletal muscle energy metabolism.
• Mitochondrial function in skeletal muscle in health and disease.
• Effect of physical (in)activity on skeletal muscle energy metabolism: from in vitro exercise, such as electrical pulse stimulation, to in vivo interventions.
• Ageing-related alterations in the metabolic function of skeletal muscle.
• Metabolites involved in inter-organ communication and regulation of energy metabolism.
• Links between regulation of ion transport and energy metabolism in skeletal muscle.
• Mechanisms underlying insulin resistance in skeletal muscle.
• Pharmacological modulation of energy metabolism in skeletal muscle.
• Mechanisms leading to dysregulation of energy metabolism in skeletal muscle in chronic inflammatory disorders, obesity, and diabetes mellitus.
• The role of skeletal muscle innervation in regulation of energy metabolism.
• Regulation of muscle mass, hypertrophy, sarcopenia and aging.
• Cancer cachexia and muscle wasting.


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Skeletal muscles can collectively be regarded as the largest organ in human body. Indeed, there are over 600 skeletal muscles, which under physiological conditions represent ~40% of body weight and ~20% of the resting metabolic rate. Skeletal muscles are a major organ for the conversion of lipids and glucose. At rest 70% of the energy consumption of muscle comes from fatty acids. Moreover, skeletal muscles are quantitatively the most important site of the postprandial insulin-stimulated glucose disposal and contain the largest body stores of glycogen, proteins, as well as potassium. In addition, they are not only the largest, but also one of the most dynamic metabolic organs, which undergoes a tremendous increase in metabolic rate, glucose uptake, and transmembrane ion transport between the resting and the actively contracting state.

Importantly, while the metabolic pathways in skeletal muscles are regulated by a plethora of factors, including metabolic hormones, contractions, reactive oxygen species, hypoxia, and NO, skeletal muscles do not just passively respond to regulatory signals. In fact, skeletal muscles are a major source of signal molecules (myokines) that participate in inter-organ crosstalk and actively modulate energy metabolism in other organs.

Given the size of skeletal muscles and a wide spectrum of metabolic functions performed by them it is not surprising that metabolic dysfunction of skeletal muscles, such as insulin resistance, disrupts systemic metabolic homeostasis. Furthermore, skeletal muscles are key players underpinning the well-established effects that regular exercise training has in human health and in the prevention or treatment of major, if not all, degenerative diseases, such as sarcopenia as well as neurodegenerative disorders, which are known to be associated with metabolic dysfunction. Pharmacological modulation of energy metabolism in skeletal muscle is therefore a promising strategy to combat chronic non-communicable diseases.

Clearly, the quest to untangle energy metabolism in skeletal muscles will not only broaden the boundaries of our understanding of physiology, but will have important practical ramifications, including development of new pharmacotherapies.

The aim of this Research Topic is to highlight recent developments in our understanding of energy metabolism in skeletal muscle under physiological and pathophysiological conditions and to facilitate the use of this knowledge on the road to the discovery of pharmacological targets and new pharmacotherapies. Different types of manuscripts, including original research, methodological studies, as well as reviews, will be considered.

The suggested topics include, but are not limited to:
• Regulation of metabolic pathways in skeletal muscle, including intracellular signalling.
• Skeletal muscle as a target and source of signal molecules, including metabolic hormones and myokines, which regulate energy metabolism and participate in cross-talk between skeletal muscles and other organs.
• Experimental models, including cell cultures and isolated organs, for investigation of skeletal muscle energy metabolism.
• Mitochondrial function in skeletal muscle in health and disease.
• Effect of physical (in)activity on skeletal muscle energy metabolism: from in vitro exercise, such as electrical pulse stimulation, to in vivo interventions.
• Ageing-related alterations in the metabolic function of skeletal muscle.
• Metabolites involved in inter-organ communication and regulation of energy metabolism.
• Links between regulation of ion transport and energy metabolism in skeletal muscle.
• Mechanisms underlying insulin resistance in skeletal muscle.
• Pharmacological modulation of energy metabolism in skeletal muscle.
• Mechanisms leading to dysregulation of energy metabolism in skeletal muscle in chronic inflammatory disorders, obesity, and diabetes mellitus.
• The role of skeletal muscle innervation in regulation of energy metabolism.
• Regulation of muscle mass, hypertrophy, sarcopenia and aging.
• Cancer cachexia and muscle wasting.


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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Submission Deadlines

26 November 2021 Abstract
25 March 2022 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

26 November 2021 Abstract
25 March 2022 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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