Functional Roles and Regulatory Factors of Histidine-Related Compounds in Skeletal Muscle Metabolism of Teleosts with Distinct Swimming Strategies.

Histidine-related compounds (HRCs) are pleiotropic, ergogenic molecules implicated in exercise performance enhancement, yet their distribution, mechanistic actions, and metabolic regulation in skeletal muscle remain poorly defined. Herein, we performed comparative analysis using three teleost fish species with distinct swimming strategies: the sustained swimmer Pseudocaranx dentex, the prolonged swimmer Takifugu rubripes, and the burst swimmer Paralichthys olivaceus. The aerobic, anaerobic, antioxidant, and buffering (βm) capacities of slow-twitch muscle (SM) and fast-twitch muscle (FM) were measured and their correlations with HRCs content were assessed. Our results confirmed that FM consistently exhibits higher anaerobic capacity and βm across all species, whereas SM possesses superior aerobic and antioxidant capacities. Species rankings for these capacities: P. dentex > T. rubripes > P. olivaceus, confirming they were effective models for investigating HRC mechanism in skeletal muscles. A significantly higher HRC content in FM, compared to SM, was observed exclusively in P. dentex, which also possessed the highest overall HRC content compared to the other species. This pattern suggests a less prominent role for HRCs in highly oxidative SM, where their content was markedly low. Strong positive correlations were identified between HRC content with both anaerobic and buffering capabilities, supporting their role as intramuscular pH regulators. Quantitative gene expression analysis further identified Slc15a4 and Slc7a2 as putative key regulators of HRCs metabolism, based on their conserved high expression in FM and strong correlation with interspecific HRCs accumulation. Collectively, our results provide a valuable insight into the role and regulation of HRCs in the skeletal muscle of teleost fishes.