{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T08:24:21Z","timestamp":1782289461104,"version":"3.54.5"},"reference-count":24,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2020,11,12]],"date-time":"2020-11-12T00:00:00Z","timestamp":1605139200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81903700"],"award-info":[{"award-number":["81903700"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81773804"],"award-info":[{"award-number":["81773804"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Fluoxetine is a first\u2010line selective serotonin reuptake inhibitor widely applied for the treatment of depression; however, it induces abnormal hepatic lipid metabolism. Considering decreased expression or function of glucose\u20106\u2010phosphatase (G6Pase), a key enzyme in gluconeogenesis, or the upregulation of fatty acid uptake, causes hepatic lipid accumulation. The aim of this study was to elucidate whether G6Pase regulation and fatty acid uptake alteration contribute to fluoxetine\u2010induced abnormal hepatic lipid metabolism. Our study revealed that 8\u2010week oral administration of fluoxetine dose\u2010dependently increased hepatic triglyceride, causing hepatic steatosis. Concomitantly, the expression of G6Pase in mouse livers and primary mouse hepatocytes (PMHs) was downregulated in a concentration\u2010dependent manner. Furthermore, fluoxetine increased the concentrations of glucose\u20106\u2010phosphate (G6Pase substrate) and acetyl CoA (the substrate for de novo lipogenesis) in mouse livers. Additionally, fluoxetine also induced lipid accumulation and downregulated G6Pase expression in HepG2 cells. However, the uptake of green fluorescent fatty acid (BODIPY\u2122 FL C16) in PMHs was not changed after fluoxetine treatment, indicating that fluoxetine\u2010induced hepatic steatosis was not associated with fatty acid uptake alteration. In conclusion, fluoxetine downregulated hepatic G6Pase expression, subsequently enhanced the transformation of glucose to lipid, and ultimately resulted in hepatic steatosis, but with no impact on fatty acid uptake.<\/jats:p>","DOI":"10.1002\/jat.4109","type":"journal-article","created":{"date-parts":[[2020,11,12]],"date-time":"2020-11-12T08:49:37Z","timestamp":1605170977000},"page":"1232-1240","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Downregulation of glucose\u20106\u2010phosphatase expression contributes to fluoxetine\u2010induced hepatic steatosis"],"prefix":"10.1002","volume":"41","author":[{"given":"Shuanghui","family":"Lu","sequence":"first","affiliation":[{"name":"Institute of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences Zhejiang University  Hangzhou 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