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This study aimed to systematically evaluate the anti-fatigue efficacy of HFOs from Antarctic krill (HFOs-AK) and explore its mechanism of action through establishing the fatigue model of endurance swimming in mice. Therefore, according to the comparison with the endurance swimming model group, HFOs-AK were able to dose-dependently prolong the endurance swimming time, reduce the levels of the metabolites (lactic acid, blood urea nitrogen, and blood ammonia), increase the content of blood glucose, muscle glycogen, and liver glycogen, reduce lactate dehydrogenase and creatine kinase extravasation, and protect muscle tissue from damage in the endurance swimming mice. HFOs-AK were shown to enhance Na+-K+-ATPase and Ca2+-Mg2+-ATPase activities and increase ATP content in muscle tissue. Meanwhile, HFOs-AK also showed significantly antioxidant ability by increasing the activities of superoxide dismutase and glutathione peroxidase in the liver and decreasing the level of malondialdehyde. Further studies showed that HFOs-AK could regulate the body\u2019s energy metabolism and thus exert its anti-fatigue effects by activating the AMPK signaling pathway and up-regulating the expression of p-AMPK and PGC-\u03b1 proteins. Therefore, HFOs-AK can be used as an auxiliary functional dietary molecules to exert its good anti-fatigue activity and be applied to anti-fatigue functional foods.<\/jats:p>","DOI":"10.3390\/md22070322","type":"journal-article","created":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T13:12:57Z","timestamp":1721394777000},"page":"322","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Systematical Investigation on Anti-Fatigue Function and Underlying Mechanism of High Fischer Ratio Oligopeptides from Antarctic Krill on Exercise-Induced Fatigue in Mice"],"prefix":"10.3390","volume":"22","author":[{"given":"Sha-Yi","family":"Mao","sequence":"first","affiliation":[{"name":"Zhejiang Provincial Engineering Technology Research Center of Marine Biomedical Products, School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan 316022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi-Kun","family":"Suo","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Engineering Technology Research Center of Marine Biomedical Products, School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan 316022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Mei","family":"Wang","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Engineering Technology Research Center of Marine Biomedical Products, School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan 316022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0922-8602","authenticated-orcid":false,"given":"Chang-Feng","family":"Chi","sequence":"additional","affiliation":[{"name":"National and Provincial Joint Engineering Research Centre for Marine Germplasm Resources Exploration and Utilization, School of Marine Science and Technology, Zhejiang Ocean University, Zhoushan 316022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2712-9045","authenticated-orcid":false,"given":"Bin","family":"Wang","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Engineering Technology Research Center of Marine Biomedical Products, School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan 316022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1007\/s11947-022-02786-4","article-title":"Isolation of immunomodulatory biopeptides from Atlantic Mackerel (Scomber scombrus) protein hydrolysate based on molecular weight, charge, and hydrophobicity","volume":"15","author":"Abachi","year":"2022","journal-title":"Food Bioprocess Technol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Hu, Y.D., Xi, Q.H., Kong, J., Zhao, Y.Q., Chi, C.F., and Wang, B. 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