Sheep skin collagen peptide exerts an anti-fatigue effect by improving energy metabolism via AMPK/PGC-1α axis and reducing oxidative damage via NRF2/HO-1 axis

The development of bioactive substances to mitigate exercise-induced fatigue is crucial for enhancing physical recovery and performance. This study explores the anti-fatigue effects and mechanisms of collagen peptides derived from sheep skin. The mechanism of anti-fatigue focuses on AMPK/PGC-1 alpha and NRF2/HO-1 pathways. These peptides, characterized by elevated levels of arginine and branched-chain amino acids, demonstrate significant anti-fatigue properties. Mice administered collagen peptides exhibited a prolonged swimming time of 15 min, reflecting a 55% increase compared to the control group (n = 8). This enhanced endurance is likely due to an increase in slow-twitch muscle fibers, which are more resistant to fatigue. Further analysis revealed that the peptide administration group showed increased expression of AMPK and PGC-1 alpha at both the gene and protein levels. Collagen peptides also promoted energy metabolism and ATP content in C2C12 muscle cells in vitro, as well as in skeletal muscle in vivo. Additionally, these peptides facilitated the nuclear accumulation of NRF2 protein and reduced the expression of Keap-1. This led to an improvement in the body's antioxidant capacity, evidenced by elevated expression of SOD, GSH-Px, and HO-1. Moreover, collagen peptides reduced MDA accumulation and enhanced mitochondrial function by activating the NRF2/HO-1 axis. Consequently, collagen peptides exhibit anti-fatigue effects through two primary mechanisms: enhancing energy metabolism via the AMPK/PGC-1 alpha axis and reducing oxidative damage through the NRF2/HO-1 axis.