Novel peptides from sea cucumber intestines hydrolyzed by neutral protease alleviate exercise‐induced fatigue via upregulating the glutaminemediated Ca2+/Calcineurin signaling pathway in mice

Abstract Sea cucumber intestines are considered a valuable resource in the sea cucumber processing industry due to their balanced amino acid composition. Studies have reported that peptides rich in glutamate and branched‐chain amino acids have anti‐fatigue properties. However, the function of the sea cucumber intestine in reducing exercise‐induced fatigue remains unclear. In this study, we enzymatically hydrolyzed low molecular weight peptides from sea cucumber intestines (SCIP) and administered SCIP orally to mice to examine its effects on exercise‐induced fatigue using swimming and pole‐climbing exhaustion experiments. The results revealed that supplementation with SCIP significantly prolonged the exhaustion time of swimming in mice, decreased blood lactate and urea nitrogen levels, and increased liver and muscle glycogen levels following a weight‐loaded swimming test. Immunofluorescence analysis indicated a notable increase the proportion of slow‐twitch muscle fiber and a significant decrease the proportion of fast‐twitch muscle fiber following SCIP supplementation. Furthermore, SCIP upregulated mRNA expression levels of Ca 2+ /Calcineurin upstream and downstream regulators, thereby contributing to the promotion of skeletal muscle fiber type conversion. This study presents the initial evidence establishing SCIP as a potential enhancer of skeletal muscle fatigue resistance, consequently providing a theoretical foundation for the valuable utilization of sea cucumber intestines.