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This study investigated the anti\u2010obesity effects of\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Akkermansia muciniphila<\/jats:italic>\n                    <\/jats:styled-content>\n                    HHAKK\u03b1 in high\u2010fat diet (HFD)\u2010induced obese mice. C57BL\/6J mice were administered HHAKK\u03b1 orally for 8\u2009weeks while maintained on HFD. Results demonstrated that HHAKK\u03b1 significantly inhibited weight gain (5.76\u2009g vs. 10.79\u2009g in HFD group), with efficacy comparable to orlistat. HHAKK\u03b1 intervention effectively maintained glucose homeostasis, decreased serum triglycerides and LDL\u2010cholesterol levels, and elevated adiponectin and GLP\u20101 levels. Furthermore, HHAKK\u03b1 significantly reduced pro\u2010inflammatory cytokines (TNF\u2010\u03b1, IL\u20101\u03b2, MCP\u20101) and alleviated hepatic steatosis and adipocyte hypertrophy. Mechanistically, HHAKK\u03b1 modulated gut microbiota composition, increasing beneficial bacteria (\n                    <jats:italic>Akkermansia<\/jats:italic>\n                    ,\n                    <jats:italic>Roseburia<\/jats:italic>\n                    ,\n                    <jats:italic>Eubacterium<\/jats:italic>\n                    ) while decreasing the Bacillota\/Bacteroidota ratio by 55.35%. Notably, the HHAKK\u03b1 intervention significantly enhanced fecal short\u2010chain fatty acids (SCFAs) production\u2014particularly butyrate, which was restored to approximately 1.5 times its normal level\u2014and this effect correlated negatively with serum lipid levels and inflammatory markers. Molecular analysis revealed that HHAKK\u03b1 regulated hepatic lipid metabolism by inhibiting FASN expression and upregulating PGC\u20101\u03b1. These findings suggest that\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>A. muciniphila<\/jats:italic>\n                    <\/jats:styled-content>\n                    HHAKK\u03b1 ameliorates HFD\u2010induced obesity through a multi\u2010faceted mechanism involving gut microbiota modulation, SCFA production enhancement, inflammation suppression, and hepatic lipid metabolism regulation, highlighting its therapeutic potential for obesity management.\n                  <\/jats:p>","DOI":"10.1096\/fj.202603191rr","type":"journal-article","created":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T07:55:31Z","timestamp":1791014131000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<i>Akkermansia muciniphila<\/i>\n                    <scp>HHAKK\u03b1<\/scp>\n                    Prevents High\u2010Fat Diet\u2010Induced Obesity in Mice via Gut Microbiota Modulation and Regulation of Hepatic Lipid Metabolism"],"prefix":"10.1096","volume":"40","author":[{"given":"Guiqiu","family":"Zhou","sequence":"first","affiliation":[{"name":"College of Food Science and Engineering Jilin Agricultural University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengling","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Food Science and Engineering Jilin Agricultural University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingling","family":"Zhao","sequence":"additional","affiliation":[{"name":"Global Research and Technology Center H&amp;H Group, H&amp;H Research  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feitong","family":"Liu","sequence":"additional","affiliation":[{"name":"Global Research and Technology Center H&amp;H Group, H&amp;H Research  Guangzhou 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