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An octapeptide (Gly-Phe-Cys-Asp-Arg-Met-Pro-Leu), termed P3-1, was isolated from macadamia nuts for the first time. This study evaluated the ameliorative effect of P3-1 on nonalcoholic fatty liver disease (NAFLD) and clarified the molecular basis of this action. The results showed that P3-1 attenuated hepatic pathological damage, improved lipid metabolism and liver function indices, and enhanced antioxidant capacity in NAFLD mice. In addition, P3-1 enhanced intestinal barrier function, thereby improving hepatic metabolic function and inflammatory status by restoring gut microbiota balance. P3-1 alleviated lipid peroxidation by activating key NAFLD-related signaling pathways involving PPAR\u03b1\/RXR\u03b1. P3-1 regulated the expression of lipid metabolism-related genes, including APOA1, FASN, SCD-1, and FABP1, and suppressed NF-\u03baB expression, thereby effectively attenuating inflammatory responses. These results indicate that P3-1 improves lipid metabolism and inflammatory status by modulating the liver\u2013gut axis and shows potential as a functional health-oriented food ingredient.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c02911","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T20:01:51Z","timestamp":1788811311000},"page":"28425-28441","source":"Crossref","is-referenced-by-count":0,"title":["P3-1 Alleviates\nNAFLD by Regulating the Liver\u2013Gut\nAxis and PPAR\u03b1\/RXR\u03b1 Pathway in Mice"],"prefix":"10.1021","volume":"74","author":[{"given":"Yao","family":"Huang","sequence":"first","affiliation":[{"name":"Guizhou University , , ,","place":["Guiyang, China, 550025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunxing","family":"Liu","sequence":"additional","affiliation":[{"name":"Guizhou University , , ,","place":["Guiyang, China, 550025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maosheng","family":"Cao","sequence":"additional","affiliation":[{"name":"Guizhou University , , ,","place":["Guiyang, China, 550025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiling","family":"Wan","sequence":"additional","affiliation":[{"name":"Guizhou University , , ,","place":["Guiyang, China, 550025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binlan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Guizhou University , , ,","place":["Guiyang, China, 550025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Yang","sequence":"additional","affiliation":[{"name":"Guizhou University , , ,","place":["Guiyang, China, 550025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Li","sequence":"additional","affiliation":[{"name":"Guizhou University , , ,","place":["Guiyang, China, 550025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rutao","family":"Lin","sequence":"additional","affiliation":[{"name":"Guizhou University , , ,","place":["Guiyang, China, 550025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Shi","sequence":"additional","affiliation":[{"name":"Guizhou University , , ,","place":["Guiyang, China, 550025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqiu","family":"Zou","sequence":"additional","affiliation":[{"name":"Guizhou University , , ,","place":["Guiyang, China, 550025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhentao","family":"Cheng","sequence":"additional","affiliation":[{"name":"Guizhou University , , ,","place":["Guiyang, China, 550025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Chunlan","sequence":"additional","affiliation":[{"name":"Guizhou University , , ,","place":["Guiyang, China, 550025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6202-3310","authenticated-orcid":true,"given":"Fujun","family":"Miao","sequence":"additional","affiliation":[{"name":"Yunnan Academy of Forestry and Grassland , ,","place":["Kunming, China, 650201"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"issue":"9","key":"2026091609084630800_cit1","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1016\/S2468-1253(22)00165-0","article-title":"The prevalence and incidence of NAFLD\nworldwide: a systematic review and meta-analysis","volume":"7","author":"Riazi","year":"2022","journal-title":"Lancet Gastroenterol. 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