{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T04:12:19Z","timestamp":1793938339321,"version":"4.8.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T00:00:00Z","timestamp":1671408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["21377062"],"award-info":[{"award-number":["21377062"]}],"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":["KYCX19_2083"],"award-info":[{"award-number":["KYCX19_2083"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,2,17]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is widely considered as the most toxic and common carcinogen in the world. Exposure to TCDD causes liver lipid metabolism disorder and steatosis. However, the molecular mechanism of TCDD-induced liver lipid accumulation is not completely clear. Here, we found that a 5\u2009\u03bcg\/kg TCDD exposure for 3\u2009weeks induced hepatocyte lipid deposition, increased CD36 expression, and promoted AMP-activated protein kinase (AMPK) \u0251 phosphorylation in the liver of C57BL\/6J mice. Furthermore, sulfo-N-succinimidyl oleate, a CD36 inhibiter, blunted TCDD-induced lipid deposition in Huh7 cells, confirming the critical role of CD36 in TCDD-induced hepatic steatosis. In terms of molecular mechanisms, we found that TCDD exposure increased reactive oxygen species (ROS) levels in Huh7 cells, which activated AMPK. Moreover, the activated AMPK upregulated CD36 expression. Therefore, we can see that the increase in CD36 expression induced by TCDD was regulated by ROS\/AMPK\/CD36 signaling pathway. Our results help to clarify the molecular mechanism of TCDD-induced hepatic steatosis.<\/jats:p>","DOI":"10.1093\/toxsci\/kfac133","type":"journal-article","created":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T22:46:25Z","timestamp":1671317185000},"page":"276-284","source":"Crossref","is-referenced-by-count":27,"title":["2,3,7,8-Tetrachlorodibenzo-p-dioxin induces liver lipid metabolism disorder via the ROS\/AMPK\/CD36 signaling pathway"],"prefix":"10.1093","volume":"191","author":[{"given":"Yewen","family":"Cong","sequence":"first","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Nantong University , Nantong, Jiangsu 226001, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujing","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Nantong University , Nantong, Jiangsu 226001, P.R. China"},{"name":"Department of Clinical Nutrition, Nantong Third People\u2019s Hospital, Affiliated Nantong Hospital 3 of Nantong University , Nantong, Jiangsu 226006, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Nantong University , Nantong, Jiangsu 226001, P.R. China"},{"name":"Haian Center for Disease Control and Prevention , Haian, Jiangsu 226600, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Nantong University , Nantong, Jiangsu 226001, P.R. China"},{"name":"Department of Clinical Nutrition, Xuzhou Children\u2019s Hospital , Xuzhou, Jiangsu 221000, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhisheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Nantong University , Nantong, Jiangsu 226001, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changming","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Nantong University , Nantong, Jiangsu 226001, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxing","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Nantong University , Nantong, Jiangsu 226001, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangfei","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Nantong University , Nantong, Jiangsu 226001, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,12,19]]},"reference":[{"key":"2023021707585777300_","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1093\/toxsci\/kfs155","article-title":"Dietary fat is a lipid source in 2,3,7,8-tetrachlorodibenzo-rho-dioxin (TCDD)-elicited hepatic steatosis in C57BL\/6 mice","volume":"128","author":"Angrish","year":"2012","journal-title":"Toxicol. Sci"},{"key":"2023021707585777300_","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1289\/ehp.94102s9157","article-title":"The mechanism of dioxin toxicity: Relationship to risk assessment","volume":"102","author":"Birnbaum","year":"1994","journal-title":"Environ. Health Perspect"},{"key":"2023021707585777300_","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1016\/S0006-291X(84)80106-0","article-title":"TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) reduces lipoprotein lipase activity in the adipose tissue of the guinea pig","volume":"122","author":"Brewster","year":"1984","journal-title":"Biochem. Biophys. Res. Commun"},{"key":"2023021707585777300_","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/S0022-2275(20)32566-9","article-title":"Human CD36 is a high affinity receptor for the native lipoproteins HDL, LDL, and VLDL","volume":"39","author":"Calvo","year":"1998","journal-title":"J. Lipid Res"},{"key":"2023021707585777300_","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1289\/ehp.1002720","article-title":"Polychlorinated biphenyls, lead, and mercury are associated with liver disease in American adults: NHANES 2003-2004","volume":"118","author":"Cave","year":"2010","journal-title":"Environ. Health Perspect"},{"key":"2023021707585777300_","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.taap.2016.12.019","article-title":"Activation of AMPK by berberine induces hepatic lipid accumulation by upregulation of fatty acid translocase CD36 in mice","volume":"316","author":"Choi","year":"2017","journal-title":"Toxicol. Appl. Pharmacol"},{"key":"2023021707585777300_","doi-asserted-by":"crossref","first-page":"15689","DOI":"10.1038\/s41598-021-95214-0","article-title":"Thioesterase induction by 2,3,7,8-tetrachlorodibenzo-p-dioxin results in a futile cycle that inhibits hepatic \u03b2-oxidation","volume":"11","author":"Cholico","year":"2021","journal-title":"Sci. Rep"},{"key":"2023021707585777300_","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1289\/EHP316","article-title":"Chronic exposure to low doses of dioxin promotes liver fibrosis development in the C57BL\/6J diet-induced obesity mouse model","volume":"125","author":"Duval","year":"2017","journal-title":"Environ. Health Perspect"},{"key":"2023021707585777300_","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1093\/toxsci\/kfv206","article-title":"2,3,7,8-Tetrachlorodibenzo-p-dioxin alters lipid metabolism and depletes immune cell populations in the jejunum of C57BL\/6 mice","volume":"148","author":"Fader","year":"2015","journal-title":"Toxicol. Sci"},{"key":"2023021707585777300_","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.envpol.2018.04.030","article-title":"Exposure to environmental level phenanthrene induces a NASH-like phenotype in new born rat","volume":"239","author":"Guo","year":"2018","journal-title":"Environ. Pollut"},{"key":"2023021707585777300_","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.bbrc.2007.01.141","article-title":"AMPK-mediated increase in myocardial long-chain fatty acid uptake critically depends on sarcolemmal CD36","volume":"355","author":"Habets","year":"2007","journal-title":"Biochem. Biophys. Res. Commun"},{"key":"2023021707585777300_","doi-asserted-by":"crossref","first-page":"17208","DOI":"10.1074\/jbc.RA118.002579","article-title":"Mitochondria-derived ROS activate AMP-activated protein kinase (AMPK) indirectly","volume":"293","author":"Hinchy","year":"2018","journal-title":"J. Biol. Chem"},{"key":"2023021707585777300_","doi-asserted-by":"crossref","first-page":"5836","DOI":"10.1074\/jbc.RA119.010244","article-title":"Glucose availability but not changes in pancreatic hormones sensitizes hepatic AMPK activity during nutritional transition in rodents","volume":"295","author":"Huet","year":"2020","journal-title":"J. Biol. Chem"},{"key":"2023021707585777300_","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.bbrc.2005.08.070","article-title":"Increased expression of PPAR\u03b3 in high fat diet-induced liver steatosis in mice","volume":"336","author":"Inoue","year":"2005","journal-title":"Biochem. Biophys. Res. Commun"},{"key":"2023021707585777300_","doi-asserted-by":"crossref","first-page":"4590","DOI":"10.1074\/jbc.M114.627026","article-title":"CD36 binds oxidized low density lipoprotein (LDL) in a mechanism dependent upon fatty acid binding","volume":"290","author":"Jay","year":"2015","journal-title":"J. Biol. Chem"},{"key":"2023021707585777300_","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1128\/MCB.00244-16","article-title":"AMPK phosphorylates desnutrin\/ATGL and hormone-sensitive lipase to regulate lipolysis and fatty acid oxidation within adipose tissue","volume":"36","author":"Kim","year":"2016","journal-title":"Mol. Cell. Biol"},{"key":"2023021707585777300_","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1289\/ehp.1509820","article-title":"Effects of developmental activation of the aryl hydrocarbon receptor by 2,3,7,8-tetrachlorodibenzo-p-dioxin on long-term self-renewal of murine hematopoietic stem cells","volume":"124","author":"Laiosa","year":"2016","journal-title":"Environ. Health Perspect"},{"key":"2023021707585777300_","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1053\/j.gastro.2010.03.033","article-title":"A novel role for the dioxin receptor in fatty acid metabolism and hepatic steatosis","volume":"139","author":"Lee","year":"2010","journal-title":"Gastroenterology"},{"key":"2023021707585777300_","doi-asserted-by":"crossref","first-page":"122588","DOI":"10.1016\/j.jhazmat.2020.122588","article-title":"TCDD promotes liver fibrosis through disordering systemic and hepatic iron homeostasis","volume":"395","author":"Li","year":"2020","journal-title":"J. Hazard. Mater"},{"key":"2023021707585777300_","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.toxlet.2007.06.003","article-title":"2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces oxidative stress, DNA strand breaks, and poly(ADP-ribose) polymerase-1 activation in human breast carcinoma cell lines","volume":"172","author":"Lin","year":"2007","journal-title":"Toxicol. Lett"},{"key":"2023021707585777300_","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s00360-005-0483-3","article-title":"Dioxin: A review of its environmental effects and its aryl hydrocarbon receptor biology","volume":"175","author":"Mandal","year":"2005","journal-title":"J. Comp. Physiol. B"},{"key":"2023021707585777300_","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.bcp.2008.10.013","article-title":"The significance of the nongenomic pathway in mediating inflammatory signaling of the dioxin-activated Ah receptor to cause toxic effects","volume":"77","author":"Matsumura","year":"2009","journal-title":"Biochem. Pharmacol"},{"key":"2023021707585777300_","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1136\/gut.2010.222844","article-title":"Hepatic fatty acid translocase CD36 upregulation is associated with insulin resistance, hyperinsulinaemia and increased steatosis in non-alcoholic steatohepatitis and chronic hepatitis C","volume":"60","author":"Miquilena-Colina","year":"2011","journal-title":"Gut"},{"key":"2023021707585777300_","doi-asserted-by":"crossref","first-page":"15268","DOI":"10.1074\/jbc.M110.211813","article-title":"Up-regulation of AMP-activated protein kinase in cancer cell lines is mediated through c-Src activation","volume":"286","author":"Mizrachy-Schwartz","year":"2011","journal-title":"J. Biol. Chem"},{"key":"2023021707585777300_","first-page":"733","article-title":"Preliminary report: 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure to humans \u2013 Seveso, Italy","volume":"37","author":"Mocarelli","year":"1988","journal-title":"MMWR Morb. Mortal. Wkly. Rep"},{"key":"2023021707585777300_","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1093\/toxsci\/kfz140","article-title":"Selective Ah receptor ligands mediate enhanced SREBP1 proteolysis to restrict lipogenesis in Sebocytes","volume":"171","author":"Muku","year":"2019","journal-title":"Toxicol. Sci"},{"key":"2023021707585777300_","doi-asserted-by":"crossref","first-page":"2988","DOI":"10.1194\/jlr.M037812","article-title":"CD36 deletion reduces VLDL secretion, modulates liver prostaglandins, and exacerbates hepatic steatosis in ob\/ob mice","volume":"54","author":"Nassir","year":"2013","journal-title":"J. Lipid Res"},{"key":"2023021707585777300_","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1021\/acs.chemrestox.6b00430","article-title":"Lipidomic evaluation of aryl hydrocarbon receptor-mediated hepatic steatosis in male and female mice elicited by 2,3,7,8-tetrachlorodibenzo-p-dioxin","volume":"30","author":"Nault","year":"2017","journal-title":"Chem. Res. Toxicol"},{"key":"2023021707585777300_","doi-asserted-by":"crossref","first-page":"4726","DOI":"10.1111\/bph.13247","article-title":"Eicosapentaenoic acid prevents TCDD-induced oxidative stress and inflammatory response by modulating MAP kinases and redox-sensitive transcription factors","volume":"172","author":"Palanisamy","year":"2015","journal-title":"Br. J. Pharmacol"},{"key":"2023021707585777300_","doi-asserted-by":"crossref","first-page":"100886","DOI":"10.1016\/j.jbc.2021.100886","article-title":"Roles of the ubiquitin ligase CUL4B and ADP-ribosyltransferase TiPARP in TCDD-induced nuclear export and proteasomal degradation of the transcription factor AHR","volume":"297","author":"Rijo","year":"2021","journal-title":"J. Biol. Chem"},{"key":"2023021707585777300_","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1016\/S0140-6736(20)32511-3","article-title":"Non-alcoholic fatty liver disease","volume":"397","author":"Powell","year":"2021","journal-title":"Lancet"},{"key":"2023021707585777300_","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1194\/jlr.M023424","article-title":"Insulin and AMPK regulate FA translocase\/CD36 plasma membrane recruitment in cardiomyocytes via Rab GAP AS160 and Rab8a Rab GTPase","volume":"53","author":"Samovski","year":"2012","journal-title":"J. Lipid Res"},{"key":"2023021707585777300_","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3109\/10408449409017919","article-title":"The toxicokinetics and metabolism of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) and their relevance for toxicity","volume":"24","author":"Van den Berg","year":"1994","journal-title":"Crit. Rev. Toxicol"},{"key":"2023021707585777300_","doi-asserted-by":"crossref","first-page":"4893","DOI":"10.7150\/thno.36037","article-title":"CD36 tango in cancer: Signaling pathways and functions","volume":"9","author":"Wang","year":"2019","journal-title":"Theranostics"},{"key":"2023021707585777300_","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1080\/10590500903310047","article-title":"An overview of the effects of dioxins and dioxin-like compounds on vertebrates, as documented in human and ecological epidemiology","volume":"27","author":"White","year":"2009","journal-title":"J. Environ. Sci. Health. C Environ. Carcinog. Ecotoxicol. Rev"},{"key":"2023021707585777300_","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1210\/en.2015-1866","article-title":"Hepatocyte-specific disruption of CD36 attenuates fatty liver and improves insulin sensitivity in HFD-fed mice","volume":"157","author":"Wilson","year":"2016","journal-title":"Endocrinology"},{"key":"2023021707585777300_","doi-asserted-by":"crossref","first-page":"4852","DOI":"10.1096\/fj.201901994R","article-title":"AMPK facilitates intestinal long-chain fatty acid uptake by manipulating CD36 expression and translocation","volume":"34","author":"Wu","year":"2020","journal-title":"FASEB J"},{"key":"2023021707585777300_","doi-asserted-by":"crossref","first-page":"G1006","DOI":"10.1152\/ajpgi.00427.2011","article-title":"Src-mediated aryl hydrocarbon and epidermal growth factor receptor cross talk stimulates colon cancer cell proliferation","volume":"302","author":"Xie","year":"2012","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol"},{"key":"2023021707585777300_","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.envres.2014.04.027","article-title":"Agent orange exposure and disease prevalence in Korean Vietnam veterans: The Korean veterans health study","volume":"133","author":"Yi","year":"2014","journal-title":"Environ. Res"},{"key":"2023021707585777300_","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1161\/CIRCRESAHA.111.255505","article-title":"AMP-activated protein kinase regulation and biological actions in the heart","volume":"111","author":"Zaha","year":"2012","journal-title":"Circ. Res"},{"key":"2023021707585777300_","doi-asserted-by":"crossref","first-page":"33154","DOI":"10.1074\/jbc.M110.143685","article-title":"Exposure to hydrogen peroxide induces oxidation and activation of AMP-activated protein kinase","volume":"285","author":"Zmijewski","year":"2010","journal-title":"J. Biol. Chem"}],"container-title":["Toxicological Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/toxsci\/advance-article-pdf\/doi\/10.1093\/toxsci\/kfac133\/48481387\/kfac133.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/toxsci\/article-pdf\/191\/2\/276\/49198918\/kfac133.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/toxsci\/article-pdf\/191\/2\/276\/49198918\/kfac133.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,18]],"date-time":"2023-03-18T08:59:03Z","timestamp":1679129943000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/toxsci\/article\/191\/2\/276\/6936419"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,19]]},"references-count":41,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,12,19]]},"published-print":{"date-parts":[[2023,2,17]]}},"URL":"https:\/\/doi.org\/10.1093\/toxsci\/kfac133","relation":{},"ISSN":["1096-6080","1096-0929"],"issn-type":[{"value":"1096-6080","type":"print"},{"value":"1096-0929","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,2,1]]},"published":{"date-parts":[[2022,12,19]]}}}