{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T21:11:14Z","timestamp":1794258674206,"version":"4.9.0"},"reference-count":31,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T00:00:00Z","timestamp":1724976000000},"content-version":"vor","delay-in-days":60,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170585"],"award-info":[{"award-number":["82170585"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010256","name":"Guangzhou Municipal Science and Technology Project","doi-asserted-by":"publisher","award":["2023A03J0955"],"award-info":[{"award-number":["2023A03J0955"]}],"id":[{"id":"10.13039\/501100010256","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012245","name":"Science and Technology Planning Project of Guangdong Province","doi-asserted-by":"publisher","award":["2023A0505010007"],"award-info":[{"award-number":["2023A0505010007"]}],"id":[{"id":"10.13039\/501100012245","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Digest Diseases"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>We aimed to investigate the role of forkhead box O1 (FoxO1) inhibitor AS1842856 (AS) in nonalcoholic steatohepatitis (NASH) mice and the potential mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Mice were given methionine\u2010choline\u2010sufficient (MCS), or methionine\u2010 and choline\u2010deficient (MCD) diet for 5\u2009weeks, along with AS (60\u2009mg\/kg) or vehicle gavage treatment (0.2\u2009mL\/day). Body and liver weight, serum triglyceride (TG), low\u2010density lipoprotein\u2010cholesterol (LDL\u2010C), high\u2010density lipoprotein\u2010cholesterol (HDL\u2010C), alanine aminotransferase (ALT), aspartate aminotransferase (AST), fasting glucose and insulin levels were measured. Liver macrophage infiltration and ileal ZO\u20101 protein expression were also detected. Interleukin (IL)\u20106, IL\u20101\u03b2, and tumor necrosis factor (TNF)\u2010\u03b1, sterol regulatory element binding protein (SREBP)\u20101c, phosphoenolpyruvate carboxykinase (PEPCK), and glucose\u20106\u2010phosphatase (G6Pase), \u03b1\u2010smooth muscle actin (SMA), recombinant collagen type III \u03b11 (Col3a1), and connective tissue growth factor (Ctgf) expressions were measured. Stool samples were collected for 16S rDNA sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to the MCD group, AS attenuated liver weight, reduced serum TG, ALT, and AST levels, increased HDL\u2010C levels, mitigated hepatic steatosis, decreased macrophage infiltration, and augmented ileal ZO\u20101 proteins in NASH mice. It also reduced the levels of IL\u20106, IL\u20101\u03b2, and TNF\u2010\u03b1, alongside with the Srebp\u20101c mRNA expression. However, no significant effects on Pepck, G6Pase, \u03b1\u2010SMA, Col3a1, or Ctgf were observed. Furthermore, AS promoted diversity and altered gut microbiota composition in NASH mice, causing increased beneficial bacteria like <jats:italic>Akkermansia muciniphila<\/jats:italic>, <jats:italic>Parabacteroides distasonis<\/jats:italic>, and <jats:italic>Prevotellamassilia<\/jats:italic>, which were associated with metabolic functions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>FoxO1 inhibitor AS ameliorated hepatic steatosis, inflammation, and intestinal dysbiosis in NASH mice, making it a potentially promising treatment for NASH.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1751-2980.13306","type":"journal-article","created":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T08:20:53Z","timestamp":1725006053000},"page":"453-462","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Inhibition of FoxO1 ameliorates hepatic steatosis and hepatitis in nonalcoholic steatohepatitis mice through regulation of gut microbiota"],"prefix":"10.1111","volume":"25","author":[{"given":"Di Wen","family":"Shou","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology Guangzhou Digestive Disease Center, Guangzhou First People's Hospital  Guangzhou Guangdong Province China"},{"name":"Department of Gastroenterology and Hepatology The Second Affiliated Hospital, School of Medicine, South China University of Technology  Guangzhou Guangdong Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Quan","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Guangzhou Digestive Disease Center, Guangzhou First People's Hospital  Guangzhou Guangdong Province China"},{"name":"Department of Gastroenterology and Hepatology The Second Affiliated Hospital, School of Medicine, South China University of Technology  Guangzhou Guangdong Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie Min","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Guangzhou Digestive Disease Center, Guangzhou First People's Hospital  Guangzhou Guangdong Province China"},{"name":"Department of Gastroenterology and Hepatology The Second Affiliated Hospital, School of Medicine, South China University of Technology  Guangzhou Guangdong Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si Qi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Guangzhou Digestive Disease Center, Guangzhou First People's Hospital  Guangzhou Guangdong Province China"},{"name":"Department of Gastroenterology and Hepatology The Second Affiliated Hospital, School of Medicine, South China University of Technology  Guangzhou Guangdong Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Guangzhou Digestive Disease Center, Guangzhou First People's Hospital  Guangzhou Guangdong Province China"},{"name":"Department of Gastroenterology and Hepatology The Second Affiliated Hospital, School of Medicine, South China University of Technology  Guangzhou Guangdong Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong Qiang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Guangzhou Digestive Disease Center, Guangzhou First People's Hospital  Guangzhou Guangdong Province China"},{"name":"Department of Gastroenterology and Hepatology The Second Affiliated Hospital, School of Medicine, South China University of Technology  Guangzhou Guangdong Province 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