{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T15:28:44Z","timestamp":1791646124458,"version":"4.3.4"},"reference-count":46,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,7,12]],"date-time":"2023-07-12T00:00:00Z","timestamp":1689120000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Pharmacological Research"],"published-print":{"date-parts":[[2023,8]]},"DOI":"10.1016\/j.phrs.2023.106851","type":"journal-article","created":{"date-parts":[[2023,7,13]],"date-time":"2023-07-13T06:26:49Z","timestamp":1689229609000},"page":"106851","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":21,"special_numbering":"C","title":["A novel HIF2A mutation causes dyslipidemia and promotes hepatic lipid accumulation"],"prefix":"10.1016","volume":"194","author":[{"given":"Feiqiong","family":"Gao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qigu","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xudong","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karel","family":"Pacak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared","family":"Rosenblum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiong","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengping","family":"Zhuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongcui","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanjuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"1","key":"10.1016\/j.phrs.2023.106851_bib1","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.jhep.2019.03.004","article-title":"Global liver disease burdens and research trends: analysis from a Chinese perspective","volume":"71","author":"Xiao","year":"2019","journal-title":"J. Hepatol."},{"issue":"6","key":"10.1016\/j.phrs.2023.106851_bib2","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1002\/hep.27406","article-title":"The global burden of liver disease: the major impact of China","volume":"60","author":"Wang","year":"2014","journal-title":"Hepatology"},{"issue":"6","key":"10.1016\/j.phrs.2023.106851_bib3","doi-asserted-by":"crossref","first-page":"517","DOI":"10.5551\/jat.15792","article-title":"Executive summary of the Japan Atherosclerosis Society (JAS) guidelines for the diagnosis and prevention of atherosclerotic cardiovascular diseases in Japan-2012 version","volume":"20","author":"Teramoto","year":"2013","journal-title":"J. Atheroscler. Thromb."},{"key":"10.1016\/j.phrs.2023.106851_bib4","doi-asserted-by":"crossref","unstructured":"Executive summary of the third report of The National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III), Jama, vol. 285(no. 19), 2001, pp. 2486\u201397.","DOI":"10.1001\/jama.285.19.2486"},{"issue":"5","key":"10.1016\/j.phrs.2023.106851_bib5","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1016\/j.jhep.2020.01.019","article-title":"The landscape of gene mutations in cirrhosis and hepatocellular carcinoma","volume":"72","author":"Muller","year":"2020","journal-title":"J. Hepatol."},{"issue":"4","key":"10.1016\/j.phrs.2023.106851_bib6","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1002\/cbf.3612","article-title":"Hypoxia as a modulator of cytochromes P450: overexpression of the cytochromes CYP2S1 and CYP24A1 in human liver cancer cells in hypoxia","volume":"39","author":"Cabrera-Cano","year":"2021","journal-title":"Cell Biochem. Funct."},{"issue":"2","key":"10.1016\/j.phrs.2023.106851_bib7","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1002\/hep.24400","article-title":"Hypoxia-inducible transcription factor 2\u03b1 promotes steatohepatitis through augmenting lipid accumulation, inflammation, and fibrosis","volume":"54","author":"Qu","year":"2011","journal-title":"Hepatology"},{"issue":"12","key":"10.1016\/j.phrs.2023.106851_bib8","doi-asserted-by":"crossref","first-page":"5510","DOI":"10.1073\/pnas.92.12.5510","article-title":"Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension","volume":"92","author":"Wang","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"issue":"5","key":"10.1016\/j.phrs.2023.106851_bib9","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1002\/hep.24256","article-title":"Hepatocyte-specific hypoxia-inducible factor-1alpha is a determinant of lipid accumulation and liver injury in alcohol-induced steatosis in mice","volume":"53","author":"Nath","year":"2011","journal-title":"Hepatology"},{"issue":"10","key":"10.1016\/j.phrs.2023.106851_bib10","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1056\/NEJMoa1205119","article-title":"Somatic HIF2A gain-of-function mutations in paraganglioma with polycythemia","volume":"367","author":"Zhuang","year":"2012","journal-title":"N. Engl. J. Med."},{"issue":"5","key":"10.1016\/j.phrs.2023.106851_bib11","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.144368","article-title":"Developmental vascular malformations in EPAS1 gain-of-function syndrome","volume":"6","author":"Rosenblum","year":"2021","journal-title":"JCI Insight"},{"issue":"4","key":"10.1016\/j.phrs.2023.106851_bib12","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.molcel.2008.04.009","article-title":"Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway","volume":"30","author":"Kaelin","year":"2008","journal-title":"Mol. Cell"},{"issue":"9","key":"10.1016\/j.phrs.2023.106851_bib13","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.tibs.2012.06.004","article-title":"Passing the baton: the HIF switch","volume":"37","author":"Koh","year":"2012","journal-title":"Trends Biochem. Sci."},{"issue":"11","key":"10.1016\/j.phrs.2023.106851_bib14","doi-asserted-by":"crossref","first-page":"2448","DOI":"10.1038\/emboj.2012.125","article-title":"The updated biology of hypoxia-inducible factor","volume":"31","author":"Greer","year":"2012","journal-title":"EMBO J."},{"issue":"5","key":"10.1016\/j.phrs.2023.106851_bib15","doi-asserted-by":"crossref","DOI":"10.3390\/cells10051016","article-title":"Integrated action of autophagy and adipose tissue triglyceride lipase ameliorates diet-induced hepatic steatosis in liver-specific PLIN2 knockout mice","volume":"10","author":"Griffin","year":"2021","journal-title":"Cells"},{"issue":"7","key":"10.1016\/j.phrs.2023.106851_bib16","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1080\/15548627.2017.1319544","article-title":"The constitutive lipid droplet protein PLIN2 regulates autophagy in liver","volume":"13","author":"Tsai","year":"2017","journal-title":"Autophagy"},{"issue":"13","key":"10.1016\/j.phrs.2023.106851_bib17","doi-asserted-by":"crossref","first-page":"2563","DOI":"10.1182\/blood-2012-10-460972","article-title":"Novel HIF2A mutations disrupt oxygen sensing, leading to polycythemia, paragangliomas, and somatostatinomas","volume":"121","author":"Yang","year":"2013","journal-title":"Blood"},{"issue":"7","key":"10.1016\/j.phrs.2023.106851_bib18","doi-asserted-by":"crossref","first-page":"5781","DOI":"10.18632\/aging.102967","article-title":"A novel germline gain-of-function HIF2A mutation in hepatocellular carcinoma with polycythemia","volume":"12","author":"Yu","year":"2020","journal-title":"Aging"},{"issue":"20","key":"10.1016\/j.phrs.2023.106851_bib19","doi-asserted-by":"crossref","first-page":"2675","DOI":"10.1101\/gad.924501","article-title":"FIH-1: a novel protein that interacts with HIF-1alpha and VHL to mediate repression of HIF-1 transcriptional activity","volume":"15","author":"Mahon","year":"2001","journal-title":"Genes Dev."},{"issue":"11","key":"10.1016\/j.phrs.2023.106851_bib20","doi-asserted-by":"crossref","first-page":"9899","DOI":"10.1074\/jbc.M312254200","article-title":"Catalytic properties of the asparaginyl hydroxylase (FIH) in the oxygen sensing pathway are distinct from those of its prolyl 4-hydroxylases","volume":"279","author":"Koivunen","year":"2004","journal-title":"J. Biol. Chem."},{"issue":"1","key":"10.1016\/j.phrs.2023.106851_bib21","doi-asserted-by":"crossref","first-page":"9241","DOI":"10.1038\/s41598-022-13284-0","article-title":"FABP5 deletion in nociceptors augments endocannabinoid signaling and suppresses TRPV1 sensitization and inflammatory pain","volume":"12","author":"Bogdan","year":"2022","journal-title":"Sci. Rep."},{"key":"10.1016\/j.phrs.2023.106851_bib22","first-page":"229","article-title":"Isolation of rat hepatocytes","volume":"320","author":"Papeleu","year":"2006","journal-title":"Methods Mol. Biol."},{"issue":"1","key":"10.1016\/j.phrs.2023.106851_bib23","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1038\/s41467-017-01965-8","article-title":"HIF drives lipid deposition and cancer in ccRCC via repression of fatty acid metabolism","volume":"8","author":"Du","year":"2017","journal-title":"Nat. Commun."},{"issue":"10","key":"10.1016\/j.phrs.2023.106851_bib24","doi-asserted-by":"crossref","first-page":"3324","DOI":"10.2337\/db14-0472","article-title":"HIF prolyl 4-hydroxylase-2 inhibition improves glucose and lipid metabolism and protects against obesity and metabolic dysfunction","volume":"63","author":"Rahtu-Korpela","year":"2014","journal-title":"Diabetes"},{"issue":"10","key":"10.1016\/j.phrs.2023.106851_bib25","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.1182\/blood-2009-05-189985","article-title":"Involvement of oxygen-sensing pathways in physiologic and pathologic erythropoiesis","volume":"114","author":"Semenza","year":"2009","journal-title":"Blood"},{"key":"10.1016\/j.phrs.2023.106851_bib26","doi-asserted-by":"crossref","unstructured":"L. Kopin, C. Lowenstein, Dyslipidemia, Ann. Intern. Med., vol. 167(no. 11), 2017, pp. ITC81\u201396.","DOI":"10.7326\/AITC201712050"},{"key":"10.1016\/j.phrs.2023.106851_bib27","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2020.104653","article-title":"Pharmacological aspects of ANGPTL3 and ANGPTL4 inhibitors: new therapeutic approaches for the treatment of atherogenic dyslipidemia","volume":"153","author":"Ruscica","year":"2020","journal-title":"Pharm. Res."},{"issue":"1","key":"10.1016\/j.phrs.2023.106851_bib28","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/hep.28431","article-title":"Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence, and outcomes","volume":"64","author":"Younossi","year":"2016","journal-title":"Hepatology"},{"issue":"5","key":"10.1016\/j.phrs.2023.106851_bib29","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.3390\/nu5051544","article-title":"Non-alcoholic fatty liver disease (NAFLD) and its connection with insulin resistance, dyslipidemia, atherosclerosis and coronary heart disease","volume":"5","author":"Gaggini","year":"2013","journal-title":"Nutrients"},{"issue":"10290","key":"10.1016\/j.phrs.2023.106851_bib30","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":"10.1016\/j.phrs.2023.106851_bib31","article-title":"Clinical characteristics and outcomes of nonalcoholic fatty liver disease-associated hepatocellular carcinoma in the United States","author":"Karim","year":"2022","journal-title":"Clin. Gastroenterol. Hepatol.: Off. Clin. Pract. J. Am. Gastroenterol. Assoc."},{"issue":"23","key":"10.1016\/j.phrs.2023.106851_bib32","doi-asserted-by":"crossref","first-page":"10839","DOI":"10.18632\/aging.102488","article-title":"HIF-2\u03b1 upregulation mediated by hypoxia promotes NAFLD-HCC progression by activating lipid synthesis via the PI3K-AKT-mTOR pathway","volume":"11","author":"Chen","year":"2019","journal-title":"Aging"},{"issue":"3","key":"10.1016\/j.phrs.2023.106851_bib33","doi-asserted-by":"crossref","first-page":"214","DOI":"10.3390\/cells8030214","article-title":"Hypoxia-inducible factors and the regulation of lipid metabolism","volume":"8","author":"Mylonis","year":"2019","journal-title":"Cells"},{"issue":"10","key":"10.1016\/j.phrs.2023.106851_bib34","doi-asserted-by":"crossref","first-page":"2553","DOI":"10.1111\/liv.14519","article-title":"Hypoxia-inducible factor 2\u03b1 drives hepatosteatosis through the fatty acid translocase CD36","volume":"40","author":"Rey","year":"2020","journal-title":"Liver Int.: Off. J. Int. Assoc. Study Liver"},{"issue":"16","key":"10.1016\/j.phrs.2023.106851_bib35","doi-asserted-by":"crossref","first-page":"4527","DOI":"10.1128\/MCB.00200-09","article-title":"Hypoxia-inducible factor 2 regulates hepatic lipid metabolism","volume":"29","author":"Rankin","year":"2009","journal-title":"Mol. Cell. Biol."},{"issue":"11","key":"10.1016\/j.phrs.2023.106851_bib36","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1038\/nm.4412","article-title":"Activation of intestinal hypoxia-inducible factor 2alpha during obesity contributes to hepatic steatosis","volume":"23","author":"Xie","year":"2017","journal-title":"Nat. Med."},{"issue":"5","key":"10.1016\/j.phrs.2023.106851_bib37","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1016\/j.cmet.2019.09.016","article-title":"Adipocyte hypoxia-inducible factor 2alpha suppresses atherosclerosis by promoting adipose ceramide catabolism","volume":"30","author":"Zhang","year":"2019","journal-title":"Cell Metab."},{"issue":"1","key":"10.1016\/j.phrs.2023.106851_bib38","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/s41574-018-0096-z","article-title":"The role of hypoxia-inducible factors in metabolic diseases","volume":"15","author":"Gonzalez","year":"2018","journal-title":"Nat. Rev. Endocrinol."},{"issue":"6","key":"10.1016\/j.phrs.2023.106851_bib39","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1158\/2159-8290.CD-14-1507","article-title":"HIF2alpha-dependent lipid storage promotes endoplasmic reticulum homeostasis in clear-cell renal cell carcinoma","volume":"5","author":"Qiu","year":"2015","journal-title":"Cancer Discov."},{"issue":"12","key":"10.1016\/j.phrs.2023.106851_bib40","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1016\/j.tem.2016.09.001","article-title":"Perilipin 2 and age-related metabolic diseases: a new perspective","volume":"27","author":"Conte","year":"2016","journal-title":"Trends Endocrinol. Metab."},{"issue":"7242","key":"10.1016\/j.phrs.2023.106851_bib41","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1038\/nature07976","article-title":"Autophagy regulates lipid metabolism","volume":"458","author":"Singh","year":"2009","journal-title":"Nature"},{"issue":"5","key":"10.1016\/j.phrs.2023.106851_bib42","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1016\/j.devcel.2009.05.001","article-title":"Lipophagy: selective catabolism designed for lipids","volume":"16","author":"Weidberg","year":"2009","journal-title":"Dev. Cell"},{"issue":"11","key":"10.1016\/j.phrs.2023.106851_bib43","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1046\/j.1440-1746.2003.03198.x","article-title":"Rodent nutritional model of non-alcoholic steatohepatitis: species, strain and sex difference studies","volume":"18","author":"Kirsch","year":"2003","journal-title":"J. Gastroenterol. Hepatol."},{"key":"10.1016\/j.phrs.2023.106851_bib44","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.plipres.2015.05.002","article-title":"Strategies, models and biomarkers in experimental non-alcoholic fatty liver disease research","volume":"59","author":"Willebrords","year":"2015","journal-title":"Prog. Lipid Res."},{"issue":"5","key":"10.1016\/j.phrs.2023.106851_bib45","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1097\/HEP.0000000000000323","article-title":"AASLD practice guidance on the clinical assessment and management of nonalcoholic fatty liver disease","volume":"77","author":"Rinella","year":"2023","journal-title":"Hepatology"},{"issue":"1","key":"10.1016\/j.phrs.2023.106851_bib46","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1111\/j.1872-034X.2007.00008.x","article-title":"Longitudinal analysis of murine steatohepatitis model induced by chronic exposure to high-fat diet","volume":"37","author":"Ito","year":"2007","journal-title":"Hepatol. Res.: Off. J. Jpn. Soc. Hepatol."}],"updated-by":[{"DOI":"10.1016\/j.phrs.2024.107135","type":"erratum","label":"Erratum","source":"publisher","updated":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T00:00:00Z","timestamp":1711929600000}}],"container-title":["Pharmacological Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1043661823002074?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1043661823002074?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T17:24:37Z","timestamp":1729099477000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1043661823002074"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8]]},"references-count":46,"alternative-id":["S1043661823002074"],"URL":"https:\/\/doi.org\/10.1016\/j.phrs.2023.106851","relation":{"erratum":[{"id-type":"doi","id":"10.1016\/j.phrs.2024.107135","asserted-by":"object"}]},"ISSN":["1043-6618"],"issn-type":[{"value":"1043-6618","type":"print"}],"subject":[],"published":{"date-parts":[[2023,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"A novel HIF2A mutation causes dyslipidemia and promotes hepatic lipid accumulation","name":"articletitle","label":"Article Title"},{"value":"Pharmacological Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.phrs.2023.106851","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 The Authors. Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"106851"}}