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

TY - JOUR

T1 - Rapid stimulation of protein synthesis in digesting snakes

T2 - Unveiling a novel gut-pancreas-muscle axis

AU - Rindom, Emil

AU - Last, Katja Bundgaard

AU - Svane, Anja

AU - Fammé, Asger

AU - Henriksen, Per G.

AU - Farup, Jean

AU - Jessen, Niels

AU - de Paoli, Frank Vincenzo

AU - Wang, Tobias

N1 - Publisher Copyright: © 2025 The Author(s). Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.

PY - 2025/2

Y1 - 2025/2

N2 - Aim: 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. Methods: 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. Results: 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. Conclusions: 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.

AB - Aim: 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. Methods: 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. Results: 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. Conclusions: 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.

KW - autophagy

KW - growth

KW - incretin

KW - insulin

KW - postprandial

KW - remodeling

UR - http://www.scopus.com/inward/record.url?scp=85216119810&partnerID=8YFLogxK

U2 - 10.1111/apha.70006

DO - 10.1111/apha.70006

M3 - Journal article

C2 - 39854152

AN - SCOPUS:85216119810

SN - 1748-1708

VL - 241

JO - Acta Physiologica

JF - Acta Physiologica

IS - 2

M1 - e70006

ER -