{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T06:44:49Z","timestamp":1775976289547,"version":"3.50.1"},"reference-count":33,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T00:00:00Z","timestamp":1757894400000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Nonalcoholic fatty liver disease (NAFLD) caused by childhood obesity has become an important public health problem, leading to hepatic fat accumulation, inflammation, hepatocyte apoptosis, and potential liver dysfunction. Kynurenine monooxygenase (KMO) is an enzyme of the kynurenine (Kyn) pathway, which is associated with various chronic diseases. Here, we investigated the effect of KMO inhibitor (RO 61\u20108048) via the kynurenine pathway for the treatment of NAFLD. In this study, C57BL\/6 mice were fed with high\u2010fat diet (HFD) and fructose\/sucrose (55%:45%) for to simulate fatty degeneration in vivo. Hepatic lipid peroxidation, steatosis, inflammasome activation and apoptosis were examined. In vitro, AML12 cells was incubated with free fatty acids (FFAs) for 24\u2009h to study the potential mechanism of RO 61\u20108048 treatment. Histopathological examination indicated that RO 61\u20108048 alleviated hepatic steatosis, lipid vacuolization, and inflammatory cell infiltration in HFD\u2010fed mice. RO 61\u20108048 significantly reduced the body weights and liver weights, and ameliorated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), High\u2010density lipoprotein cholesterol (HDL\u2010C), Low density lipoprotein cholesterol (LDL\u2010C) and produce quinolinic acid (QUIN) levels in C57BL\/6 mice. Compared to HFD\u2010fed mice, RO 61\u20108048 alleviated release of inflammatory cytokines (tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1), interleukin (IL)\u22121\u03b2, IL\u20106) and hepatic apoptosis. A dual luciferase reporter assay suggested the interaction between SP3 and KMO promoter. Consistent with the in\n                    <jats:italic>vivo<\/jats:italic>\n                    results, RO 61\u20108048 alleviated lipid droplet accumulation and reduced lipid reactive oxygen species (ROS) levels and apoptosis in AML12 cells. Collectively, our study demonstrates that transcription factor specificity protein 3 (SP3) is able to bind with the promoter of KMO. The KMO inhibitor (RO 61\u20108048) ameliorates lipid metabolism, inflammatory injury and hepatocyte apoptosis in NAFLD through the tryptophan\u2010kynurenine pathway, potentially serving as a promising candidate for alleviating NAFLD.\n                  <\/jats:p>","DOI":"10.1002\/jbt.70511","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T15:50:41Z","timestamp":1757951441000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Kynurenine 3\u2010hydroxylase Inhibitor RO 61\u20108048 Alleviates Nonalcoholic Fatty Liver Disease in High\u2010Fat Diet\u2010Induced Obese Mice"],"prefix":"10.1002","volume":"39","author":[{"given":"Yang","family":"Liu","sequence":"first","affiliation":[{"name":"School of Basic Medicine Jiamusi University Jiamusi Heilongjiang 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