Hungry for your alanine: when liver depends on muscle proteolysis

Fasting requires complex endocrine and metabolic interorgan crosstalk, which involves shifting from glucose to fatty acid oxidation, derived from adipose tissue lipolysis, in order to preserve glucose for the brain. The glucose-alanine (Cahill) cycle is critical for regenerating glucose. In this issue of JCI, Petersen et al. report on their use of an innovative stable isotope tracer method to show that skeletal muscle-derived alanine becomes rate controlling for hepatic mitochondrial oxidation and, in turn, for glucose production during prolonged fasting. These results provide new insight into skeletal muscle-liver metabolic crosstalk during the fed-to-fasting transition in humans.