{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:04:03Z","timestamp":1785402243229,"version":"3.56.0"},"reference-count":46,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Northwest A&F University Start-up Funding","award":["2190022005"],"award-info":[{"award-number":["2190022005"]}]},{"award":["2190022005"],"award-info":[{"award-number":["2190022005"]}],"id":[{"id":"https:\/\/ror.org\/0051rme32","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Frontier Interdisciplinary Innovation Team Construction Project in Immunobiology","award":["1080524003"],"award-info":[{"award-number":["1080524003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background: Metabolic dysfunction-associated steatohepatitis (MASH), the progressive stage of metabolic dysfunction-associated steatotic liver disease (MASLD), is characterized by hepatic steatosis, inflammation, and fibrosis, yet no specific therapy has been established. This study evaluated the therapeutic potential of Andrias davidianus liver-derived peptides (ALPs) in a mouse model of MASH. Methods: ALPs were prepared by enzymatic hydrolysis of fresh Andrias davidianus liver. A MASH model was induced in mice using a methionine- and choline-deficient diet (MRCD). ALP was administered via oral gavage, and its effects were assessed through histological staining (H&amp;E, Oil Red O, and Sirius Red), immunofluorescence (Ki67), apoptosis detection (TUNEL), serum biochemistry, and RNA-sequencing of liver tissues. Gut microbiota composition was also analyzed. Results: ALP treatment significantly alleviated hepatic histopathological features, including steatosis, inflammation, and fibrosis. It reduced aberrant proliferation and apoptosis of hepatocyte-like cells, and markedly improved serum biochemical markers of liver function. RNA-seq analysis revealed that ALP modulated the expression of lipid metabolism-related genes, an effect associated with suppression of the PPAR\u03b3 signaling pathway. Furthermore, ALP selectively modulated MRCD-induced gut microbiota dysbiosis, particularly by reducing the Firmicutes-to-Bacteroidota (F\/B) ratio and enriching Akkermansia. No overt toxicity was observed in other organs. Conclusions: Our findings demonstrate that ALP exerts protective effects against MASH by improving lipid metabolism, partially through suppression of the PPAR\u03b3 signaling pathway, and by selectively modulating specific gut microbial taxa. ALP represents a promising natural therapeutic candidate for MASH.<\/jats:p>","DOI":"10.3390\/metabo16080532","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T11:45:26Z","timestamp":1785239126000},"page":"532","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Andrias davidianus Liver-Derived Peptides Ameliorate MASH Accompanied by Attenuation of PPAR\u03b3 Signaling and Selective Modulation of Gut Microbiota"],"prefix":"10.3390","volume":"16","author":[{"given":"Xing","family":"Shen","sequence":"first","affiliation":[{"name":"Department of Biomedicine, Institute of Future Agriculture, Northwest A&F University, Yangling 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Na","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Institute of Future Agriculture, Northwest A&F University, Yangling 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Xiao","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Institute of Future Agriculture, Northwest A&F University, Yangling 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen-Yu","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Institute of Future Agriculture, Northwest A&F University, Yangling 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si-Jia","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Institute of Future Agriculture, Northwest A&F University, Yangling 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Institute of Future Agriculture, Northwest A&F University, Yangling 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-Jie","family":"He","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Institute of Future Agriculture, Northwest A&F University, Yangling 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai-Kun","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Institute of Future Agriculture, Northwest A&F University, Yangling 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing-Zhu","family":"Sun","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7311-4340","authenticated-orcid":false,"given":"Tai","family":"An","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Institute of Future Agriculture, Northwest A&F University, Yangling 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Institute of Future Agriculture, Northwest A&F University, Yangling 712100, China"},{"name":"State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi\u2019an 710032, China"},{"name":"Tangdu Innovative Institute of Science and Technology, Tangdu Hospital, Fourth Military Medical University, Xi\u2019an 710038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S32","DOI":"10.3350\/cmh.2024.0431","article-title":"Epidemiology of Metabolic Dysfunction-Associated Steatotic Liver Disease","volume":"31","author":"Younossi","year":"2025","journal-title":"Clin. 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