Understanding the role of glycine in the control of skeletal muscle mass during sepsis
Sepsis is a potentially fatal medical condition characterised by whole-body inflammation and organ failure associated with rapid and progressive muscle wasting and weakness. This muscle atrophy is life-threatening, leading to prolonged hospitalisation, morbidity and mortality. Inflammation impairs skeletal muscle protein metabolism, making it unresponsive to normal anabolic stimuli, especially nutrition. Interventions delivered early in sepsis/critical illness may be key to minimizing long-term morbidity and protracted impairments in physical function. Therefore, there is considerable interest in the development of alternative nutritional strategies that can modulate inflammation and improve muscle protein metabolism in these patients. Our preliminary data and published work reveal that a nutritional intervention with the amino acid glycine is a novel and effective strategy to reduce muscle wasting during sepsis. Utilising our cell culture, as well as mouse models of sepsis we will: define the direct effect of glycine on skeletal muscle cell metabolism in vitro; assess whether glycine can reduce muscle loss in mouse models of sepsis in vivo. These studies will fully examine the therapeutic potential of glycine administration to counteract sepsis-induced muscle wasting.
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