{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T09:04:22Z","timestamp":1781082262321,"version":"3.54.1"},"reference-count":43,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Graphene oxide (GO) as typical 2D nanomaterials (NMs) have various applications, but their long\u2010term neurological effects, particularly under health conditions like obesity, are unknown. This study investigated the chronic neurotoxicity of GO in zebrafish, both alone and in combination with high\u2010fat diet (HFD)\u2013induced obesity. Zebrafish were exposed to 0.01 or 0.1\u2009mg\/L GO for up to 3\u2009months to establish a chronic exposure regimen. Subsequently, the co\u2010exposure group was treated with HFD and 0.1\u2009mg\/L GO for 3\u2009months. Our results showed that chronic exposure to GO induced subtle alterations in locomotor behavior, and HFD\u2009+\u2009GO co\u2010exposure resulted in neurobehavioral impairment similar to HFD alone. Histopathological analysis revealed significant brain damage particularly in the HFD\u2009+\u2009GO co\u2010exposure group. RNA\u2010sequencing data revealed that co\u2010exposure uniquely perturbed the inositol phosphate metabolism pathway, as well as 13 gene ontology terms related to metabolic processes, including phosphatidylinositol, glycerophospholipid, glycerolipid, and purine nucleotide metabolism. We further verified that the co\u2010exposure upregulated the protein levels of HIF\u20101\u03b1, LDHA, and caspase\u20103, as well as key genes involved in glycolysis. This study demonstrates that chronic low\u2010dose GO exposure can induce neurobehavioral changes and neuropathology in zebrafish, and HFD\u2010induced obesity exacerbated HIF\u20101\u2013mediated metabolic pathway changes, suggesting a combined or additive effect on specific neuropathological and molecular endpoints. These findings highlight the importance of considering underlying metabolic conditions, such as obesity, for the assessment of environmental health risks of NMs.<\/jats:p>","DOI":"10.1002\/jat.70276","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T08:49:42Z","timestamp":1781081382000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Combined Effects of Chronic Graphene Oxide Exposure and High\u2010Fat Diet\u2013Induced Obesity on Neurotoxicity in Zebrafish: Behavioral, Histopathological, and HIF\u20101\u2013Mediated Metabolic Pathway Changes"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-1927-1492","authenticated-orcid":false,"given":"Lu","family":"Gan","sequence":"first","affiliation":[{"name":"Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School University of South China  Hengyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxinyu","family":"Ning","sequence":"additional","affiliation":[{"name":"Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School University of South China  Hengyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Liu","sequence":"additional","affiliation":[{"name":"Xiangtan Disease Control Center  Xiangtan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1279-5491","authenticated-orcid":false,"given":"Yi","family":"Cao","sequence":"additional","affiliation":[{"name":"Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School University of South China  Hengyang 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