Rapid stimulation of protein synthesis in digesting snakes: Unveiling a novel gut-pancreas-muscle axis

Snakes exhibit remarkable physiological shifts when their large meals induce robust postprandial growth after prolonged fasting. To understand the regulatory mechanisms underlying this rapid metabolic transition, we examined the regulation of protein synthesis in pythons, focusing on processes driving early postprandial tissue remodeling and growth.

Using the SUnSET method with puromycin labeling, we measured in vivo protein synthesis in fasting and digesting snakes at multiple post-feeding intervals. Pyloric ligation, pancreatectomy, and plasma transfusions were performed to explore the roles of gastrointestinal luminal signaling and pancreatic function across key tissues.

We observed profound and early stimulation of protein synthesis in gastrointestinal tissues and skeletal muscle already 3 h after ingestion, before any measurable rise in plasma amino acids from the meal. The gastrointestinal stimulation appears to be driven by luminal factors, while the stimulation of skeletal muscle protein synthesis is humoral with pancreatic insulin release as an integral mediator. The pre-absorptive anabolic activity is supported by the release of amino acids from the breakdown of endogenous proteins.

Our findings suggest that snakes initiate protein synthesis via distinct, tissue-specific pathways preceding nutrient absorption. This "pay before pumping" model shows how early protein synthesis prepares the digestive and muscular systems for later nutrient assimilation and growth. This intricate humoral regulation, involving a gut-pancreas-muscle axis, governs postprandial protein synthesis in snakes and provides insights into fundamental mechanisms driving metabolic adaptations and broader hyperplastic and hypertrophic responses.