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Using zebrafish model, this study aims to determine the mechanism by which Amuc_1100 reduces HFD-induced hepatic lipid accumulation through modulation of gut microbiota.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In main study, 1-month-old zebrafish were fed a low-fat diet (LFD), HFD, or HFD supplemented with 0.01% Amuc_1100 (AM0.01) for 4 weeks. Body weight gain, hepatic lipid accumulation, microbial translocation, and gut microbiota composition were evaluated. In parallel, larvae at 5\u00a0d post-fertilization were fed the same diets for 7 d and analyzed by Oil Red O staining. In validation experiments, germ-free (GF) zebrafish received microbiota transplants from donor fish fed HFD or AM0.01. Antibiotics (ABS)-treated zebrafish were fed LFD, HFD, or AM0.01 for 4 weeks. Intestinal protein interacting with Amuc_1100 was identified via pull-down and co-immunoprecipitation, and its role was confirmed using protein-protein interaction (PPI) inhibitor BV02 and gene knockdown. Data were analyzed by Student\u2019s\n                      <jats:italic>t<\/jats:italic>\n                      -test or one-way ANOVA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Compared with HFD group, zebrafish in AM0.01 group showed lower body weight gain, reduced hepatic lipid accumulation, and decreased microbial translocation (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05). AM0.01 feeding increased\n                      <jats:italic>Bacillus<\/jats:italic>\n                      abundance while reducing\n                      <jats:italic>Acinetobacter<\/jats:italic>\n                      ,\n                      <jats:italic>Plesiomonas<\/jats:italic>\n                      and\n                      <jats:italic>Aeromonas<\/jats:italic>\n                      abundances relative to HFD (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05). GF zebrafish colonized with microbiota from AM0.01-fed donors showed less hepatic lipid accumulation than those receiving microbiota from HFD-fed donors (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05). In contrast, ABS-treated zebrafish showed no significant difference in hepatic triacylglycerol content between HFD and AM0.01 groups (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&gt;\u20090.05). Using pull-down assays with intestinal proteins from LFD-fed zebrafish, we identified 14-3-3\u03b2\/\u03b1-A as an interacting protein of Amuc_1100. When 14-3-3\u03b2\/\u03b1-A PPI was inhibited by BV02, Amuc_1100 failed to alter the HFD-induced gut microbiota profile in 1-month-old zebrafish (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&gt;\u20090.05). Moreover, either BV02 treatment or 14-3-3\u03b2\/\u03b1-A knockdown abolished the protective effect of Amuc_1100 against hepatic lipid accumulation in conventional and GF zebrafish (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Amuc_1100 reduces hepatic lipid accumulation by modulating gut microbiota through intestinal 14-3-3\u03b2\/\u03b1-A, highlighting its potential as a therapeutic target.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40104-026-01418-7","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T23:02:15Z","timestamp":1781046135000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Amuc_1100 alleviates HFD-induced hepatic lipid accumulation via gut microbiota in zebrafish: insights from the role of intestinal 14-3-3\u03b2\/\u03b1-A"],"prefix":"10.1186","volume":"17","author":[{"given":"Qianwen","family":"Ding","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruobing","family":"Lou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shangshang","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihui","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Ran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yalin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliana","family":"Carnevali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengli","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhigang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"key":"1418_CR1","unstructured":"Fishery Bureau of Agriculture Ministry of China. 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