Abstract
Due to its essential role in movement, insulating the internal organs, generating heat to maintain core body temperature, and acting as a major energy storage depot, any impairment to skeletal muscle structure and function may lead to an increase in both morbidity and mortality. In the context of skeletal muscle, altered metabolism is directly associated with numerous pathologies and disorders, including diabetes, and obesity, while many skeletal muscle pathologies have secondary changes in metabolism, including cancer cachexia, sarcopenia and the muscular dystrophies. Furthermore, the importance of cellular metabolism in the regulation of skeletal muscle stem cells is beginning to receive significant attention. Thus, it is clear that skeletal muscle metabolism is intricately linked to the regulation of skeletal muscle mass and regeneration. The aim of this review is to discuss some of the recent findings linking a change in metabolism to changes in skeletal muscle mass, as well as describing some of the recent studies in developmental, cancer and stem-cell biology that have identified a role for cellular metabolism in the regulation of stem cell function, a process termed “metabolic reprogramming.”
Highlights
Metabolism is loosely defined as the collection of enzymatic reactions essential for life, and can be catabolic/anabolic and exothermic/endothermic in nature
A detailed discussion about how cells sense amino acids (AAs) and how these signals are communicated to mTORC1 is beyond the scope of this review as we aim to focus in more detail how changes in glucose metabolism alter the activity of this particular pathway, instead the reader is directed to a number of recent excellent reviews (Dodd and Tee, 2012; Laplante and Sabatini, 2012)
HMGB1administration resulted in a reduction in the protein expression of pyruvate kinase muscle (PKM) isoform 1 leading to a reduction in PKM activity, which was associated with a reduced phosphorylation status of mechanistic target of rapamycin (mTOR), increased autophagy, and increased utilization of AAs, glutamine in particular, to produce intermediates for the tricarboxylic acid cycle (TCA) cycle (Luo et al, 2013)
Summary
Metabolism is loosely defined as the collection of enzymatic reactions essential for life, and can be catabolic/anabolic and exothermic/endothermic in nature. As cellular metabolism is beginning to receive increased attention in the regulation of stem cell identity, we discuss some of the implications for the regulation of skeletal muscle stem cell activity and regeneration following injury. Before addressing these topics in detail, a brief overview of the major metabolic pathways will be discussed. CELLULAR METABOLISM IN SKELETAL MUSCLE Energy in the form of adenosine triphosphate (ATP) is essential for cells to conduct the processes necessary for life, and depletion of ATP can lead to necrosis or apoptosis (Tsujimoto, 1997). FAO involves a stepwise process of dehydrogenation of acyl-CoA to acetyl-CoA which can be metabolized by the tricarboxylic acid cycle (TCA) and the mitochondrial electron transport chain (ETC, Salway, 2012, Figure 1)
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