Hypothesis: Muscular glutamine deficiency in sepsis—A necessary step for a hibernation-like state?

Glutamine depletion in skeletal muscle of severely ill patients is an outstanding metabolic marker related to acute skeletal muscle wasting. To date it is unclear why intracellular glutamine concentrations are lowered in skeletal muscle to such an extent when simultaneously muscular glutamine synthesis and release are stimulated. This essay introduces a hypothesis that intracellular glutamine deficiency is part of a metabolic program maintaining cell integrity. This program seems to resemble short-term hibernation, which can be observed in various mammalian species during periods of starvation. Interestingly, even in septic patients who do not survive, there are no signs of apoptosis or necrosis in affected organs. Therefore, in severe illness evolutionarily conserved energy saving programs may be switched on for protecting the organs in a mode reminiscent of hibernation. This would explain the low energy expenditure as described for septic patients and the limited success of nutrition in avoiding skeletal muscle atrophy in sepsis.