{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T18:51:24Z","timestamp":1793299884897,"version":"4.5.0"},"reference-count":44,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T00:00:00Z","timestamp":1731974400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170829"],"award-info":[{"award-number":["82170829"]}],"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":["82400529"],"award-info":[{"award-number":["82400529"]}],"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":["82170827"],"award-info":[{"award-number":["82170827"]}],"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":["81970751"],"award-info":[{"award-number":["81970751"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010562","name":"Yangtze River Scientific Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010562","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["23PJ1410700"],"award-info":[{"award-number":["23PJ1410700"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007219","name":"Natural Science Foundation of Shanghai Municipality","doi-asserted-by":"publisher","award":["22ZR1450100"],"award-info":[{"award-number":["22ZR1450100"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007219","name":"Natural Science Foundation of Shanghai Municipality","doi-asserted-by":"publisher","award":["22002400600"],"award-info":[{"award-number":["22002400600"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Metabolism"],"published-print":{"date-parts":[[2025,1]]},"DOI":"10.1016\/j.molmet.2024.102075","type":"journal-article","created":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T19:11:55Z","timestamp":1732648315000},"page":"102075","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"special_numbering":"C","title":["Leupaxin promotes hepatic gluconeogenesis and glucose metabolism by coactivation with hepatic nuclear factor 4\u03b1"],"prefix":"10.1016","volume":"91","author":[{"given":"Xiaomin","family":"Luo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijun","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caizhi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruhui","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyin","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofang","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongde","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.molmet.2024.102075_bib1","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/S2213-8587(17)30181-X","article-title":"Diabetes in sub-Saharan Africa: from clinical care to health policy","volume":"5","author":"Atun","year":"2017","journal-title":"Lancet Diabetes Endocrinol"},{"key":"10.1016\/j.molmet.2024.102075_bib2","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/S2213-8587(17)30097-9","article-title":"The global economic burden of diabetes in adults aged 20-79 years: a cost-of-illness study","volume":"5","author":"Bommer","year":"2017","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"Suppl 2","key":"10.1016\/j.molmet.2024.102075_bib3","doi-asserted-by":"crossref","first-page":"S14","DOI":"10.1007\/PL00002934","article-title":"Mortality and causes of death in the WHO multinational study of vascular disease in diabetes","volume":"44","author":"Morrish","year":"2001","journal-title":"Diabetologia"},{"key":"10.1016\/j.molmet.2024.102075_bib4","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1038\/nrd.2016.151","article-title":"Targeting hepatic glucose metabolism in the treatment of type 2 diabetes","volume":"15","author":"Rines","year":"2016","journal-title":"Nat Rev Drug Discov"},{"key":"10.1016\/j.molmet.2024.102075_bib5","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.cell.2017.03.001","article-title":"Selective chemical inhibition of PGC-1alpha gluconeogenic activity ameliorates type 2 diabetes","volume":"169","author":"Sharabi","year":"2017","journal-title":"Cell"},{"key":"10.1016\/j.molmet.2024.102075_bib6","first-page":"787","article-title":"Pathogenesis of type 2 diabetes mellitus","volume":"88","author":"DeFronzo","year":"2004","journal-title":"Med Clin"},{"key":"10.1016\/j.molmet.2024.102075_bib7","doi-asserted-by":"crossref","first-page":"286","DOI":"10.3945\/an.112.002089","article-title":"Regulation of hepatic glucose uptake and storage in\u00a0vivo","volume":"3","author":"Moore","year":"2012","journal-title":"Adv Nutr"},{"key":"10.1016\/j.molmet.2024.102075_bib8","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/s41575-022-00707-6","article-title":"Intestinal gluconeogenesis: metabolic benefits make sense in the light of evolution","volume":"20","author":"Gautier-Stein","year":"2023","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"10.1016\/j.molmet.2024.102075_bib9","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1038\/nrendo.2017.80","article-title":"Regulation of hepatic glucose metabolism in health and disease","volume":"13","author":"Petersen","year":"2017","journal-title":"Nat Rev Endocrinol"},{"key":"10.1016\/j.molmet.2024.102075_bib10","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1016\/j.cmet.2022.10.001","article-title":"The past, present, and future physiology and pharmacology of glucagon","volume":"34","author":"Capozzi","year":"2022","journal-title":"Cell Metabol"},{"key":"10.1016\/j.molmet.2024.102075_bib11","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/s41574-023-00817-4","article-title":"Revisiting the role of glucagon in health, diabetes mellitus and other metabolic diseases","volume":"19","author":"Haedersdal","year":"2023","journal-title":"Nat Rev Endocrinol"},{"key":"10.1016\/j.molmet.2024.102075_bib12","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2020.104840","article-title":"18beta-Glycyrrhetinic acid acts through hepatocyte nuclear factor 4 alpha to modulate lipid and carbohydrate metabolism","volume":"157","author":"Yang","year":"2020","journal-title":"Pharmacol Res"},{"key":"10.1016\/j.molmet.2024.102075_bib13","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.molmet.2017.10.010","article-title":"PGC-1alpha functions as a co-suppressor of XBP1s to regulate glucose metabolism","volume":"7","author":"Lee","year":"2018","journal-title":"Mol Metabol"},{"key":"10.1016\/j.molmet.2024.102075_bib14","doi-asserted-by":"crossref","DOI":"10.1038\/cddis.2017.392","article-title":"H19 lncRNA alters methylation and expression of Hnf4alpha in the liver of metformin-exposed fetuses","volume":"8","author":"Deng","year":"2017","journal-title":"Cell Death Dis"},{"key":"10.1016\/j.molmet.2024.102075_bib15","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/35093050","article-title":"Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1","volume":"413","author":"Yoon","year":"2001","journal-title":"Nature"},{"key":"10.1016\/j.molmet.2024.102075_bib16","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1038\/nature01667","article-title":"Insulin-regulated hepatic gluconeogenesis through FOXO1-PGC-1alpha interaction","volume":"423","author":"Puigserver","year":"2003","journal-title":"Nature"},{"key":"10.1016\/j.molmet.2024.102075_bib17","doi-asserted-by":"crossref","first-page":"2266","DOI":"10.1172\/JCI66062","article-title":"Dexamethasone-induced Kruppel-like factor 9 expression promotes hepatic gluconeogenesis and hyperglycemia","volume":"129","author":"Cui","year":"2019","journal-title":"J\u00a0Clin Invest"},{"key":"10.1016\/j.molmet.2024.102075_bib18","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1038\/s41419-023-05726-y","article-title":"Septin11 promotes hepatocellular carcinoma cell motility by activating RhoA to regulate cytoskeleton and cell adhesion","volume":"14","author":"Fu","year":"2023","journal-title":"Cell Death Dis"},{"key":"10.1016\/j.molmet.2024.102075_bib19","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/s41392-022-01107-7","article-title":"p53 positively regulates the proliferation of hepatic progenitor cells promoted by laminin-521","volume":"7","author":"Ma","year":"2022","journal-title":"Signal Transduct Targeted Ther"},{"key":"10.1016\/j.molmet.2024.102075_bib20","doi-asserted-by":"crossref","DOI":"10.1016\/j.compbiomed.2022.105537","article-title":"A\u00a0protein coupling and molecular simulation analysis of the clinical mutants of androgen receptor revealed a higher binding for Leupaxin, to increase the prostate cancer invasion and motility","volume":"146","author":"Khan","year":"2022","journal-title":"Comput Biol Med"},{"key":"10.1016\/j.molmet.2024.102075_bib21","doi-asserted-by":"crossref","first-page":"2418","DOI":"10.1038\/s41375-022-01687-x","article-title":"Protein tyrosine kinase 2b inhibition reverts niche-associated resistance to tyrosine kinase inhibitors in AML","volume":"36","author":"Allert","year":"2022","journal-title":"Leukemia"},{"key":"10.1016\/j.molmet.2024.102075_bib22","doi-asserted-by":"crossref","DOI":"10.1172\/JCI166333","article-title":"Phenotype screens of murine pancreatic cancer identify a Tgf-alpha-Ccl2-paxillin axis driving human-like neural invasion","volume":"133","author":"Wang","year":"2023","journal-title":"J\u00a0Clin Invest"},{"key":"10.1016\/j.molmet.2024.102075_bib23","doi-asserted-by":"crossref","first-page":"466","DOI":"10.3389\/fimmu.2020.00466","article-title":"Leupaxin expression is dispensable for B cell immune responses","volume":"11","author":"Bonaud","year":"2020","journal-title":"Front Immunol"},{"key":"10.1016\/j.molmet.2024.102075_bib24","doi-asserted-by":"crossref","DOI":"10.3389\/fcell.2020.605744","article-title":"Clinicopathological significances of cancer stem cell-associated HHEX expression in breast cancer","volume":"8","author":"Zhang","year":"2020","journal-title":"Front Cell Dev Biol"},{"key":"10.1016\/j.molmet.2024.102075_bib25","doi-asserted-by":"crossref","first-page":"8316","DOI":"10.1074\/jbc.274.12.8316","article-title":"Cloning and characterization of androgen receptor coactivator, ARA55, in human prostate","volume":"274","author":"Fujimoto","year":"1999","journal-title":"J\u00a0Biol Chem"},{"key":"10.1016\/j.molmet.2024.102075_bib26","first-page":"4927","article-title":"The Group 3 LIM domain protein paxillin potentiates androgen receptor transactivation in prostate cancer cell lines","volume":"63","author":"Kasai","year":"2003","journal-title":"Cancer Res"},{"key":"10.1016\/j.molmet.2024.102075_bib27","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1091\/mbc.02-06-0099","article-title":"Hic-5 communicates between focal adhesions and the nucleus through oxidant-sensitive nuclear export signal","volume":"14","author":"Shibanuma","year":"2003","journal-title":"Mol Biol Cell"},{"key":"10.1016\/j.molmet.2024.102075_bib28","doi-asserted-by":"crossref","first-page":"6791","DOI":"10.1038\/onc.2008.291","article-title":"Smad7 is inactivated through a direct physical interaction with the LIM protein Hic-5\/ARA55","volume":"27","author":"Wang","year":"2008","journal-title":"Oncogene"},{"key":"10.1016\/j.molmet.2024.102075_bib29","doi-asserted-by":"crossref","first-page":"5154","DOI":"10.1074\/jbc.M411575200","article-title":"Novel function of androgen receptor-associated protein 55\/Hic-5 as a negative regulator of Smad3 signaling","volume":"280","author":"Wang","year":"2005","journal-title":"J\u00a0Biol Chem"},{"key":"10.1016\/j.molmet.2024.102075_bib33","doi-asserted-by":"crossref","first-page":"527","DOI":"10.4161\/cam.4.4.12399","article-title":"Leupaxin is similar to paxillin in focal adhesion targeting and tyrosine phosphorylation but has distinct roles in cell adhesion and spreading","volume":"4","author":"Chen","year":"2010","journal-title":"Cell Adhes Migrat"},{"key":"10.1016\/j.molmet.2024.102075_bib34","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1111\/j.1349-7006.2009.01398.x","article-title":"LIM domain-containing adaptor, leupaxin, localizes in focal adhesion and suppresses the integrin-induced tyrosine phosphorylation of paxillin","volume":"101","author":"Tanaka","year":"2010","journal-title":"Cancer Sci"},{"key":"10.1016\/j.molmet.2024.102075_bib35","doi-asserted-by":"crossref","first-page":"27181","DOI":"10.1074\/jbc.M704625200","article-title":"Leupaxin negatively regulates B cell receptor signaling","volume":"282","author":"Chew","year":"2007","journal-title":"J\u00a0Biol Chem"},{"key":"10.1016\/j.molmet.2024.102075_bib36","doi-asserted-by":"crossref","first-page":"106","DOI":"10.3892\/ijo.2015.2988","article-title":"Leupaxin is expressed in mammary carcinoma and acts as a transcriptional activator of the estrogen receptor alpha","volume":"47","author":"Kaulfuss","year":"2015","journal-title":"Int J Oncol"},{"key":"10.1016\/j.molmet.2024.102075_bib37","doi-asserted-by":"crossref","first-page":"2313","DOI":"10.1007\/s13277-015-4060-4","article-title":"Regulation of beta-catenin transcription activity by leupaxin in hepatocellular carcinoma","volume":"37","author":"Shi","year":"2016","journal-title":"Tumour Biol"},{"key":"10.1016\/j.molmet.2024.102075_bib38","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/s12272-013-0018-5","article-title":"Transcriptional regulators of hepatic gluconeogenesis","volume":"36","author":"Oh","year":"2013","journal-title":"Arch Pharm Res (Seoul)"},{"key":"10.1016\/j.molmet.2024.102075_bib39","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1016\/j.molcel.2023.02.007","article-title":"Histone phosphorylation integrates the hepatic glucagon-PKA-CREB gluconeogenesis program in response to fasting","volume":"83","author":"Zhao","year":"2023","journal-title":"Mol Cell"},{"key":"10.1016\/j.molmet.2024.102075_bib40","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1016\/j.apsb.2021.09.031","article-title":"PXR activation impairs hepatic glucose metabolism partly via inhibiting the HNF4alpha-GLUT2 pathway","volume":"12","author":"Liu","year":"2022","journal-title":"Acta Pharm Sin B"},{"key":"10.1016\/j.molmet.2024.102075_bib41","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2023.1197063","article-title":"Structural insights into the HNF4 biology","volume":"14","author":"Beinsteiner","year":"2023","journal-title":"Front Endocrinol"},{"key":"10.1016\/j.molmet.2024.102075_bib42","doi-asserted-by":"crossref","first-page":"32432","DOI":"10.1074\/jbc.M806179200","article-title":"A\u00a0combination of HNF-4 and Foxo1 is required for reciprocal transcriptional regulation of glucokinase and glucose-6-phosphatase genes in response to fasting and feeding","volume":"283","author":"Hirota","year":"2008","journal-title":"J\u00a0Biol Chem"},{"key":"10.1016\/j.molmet.2024.102075_bib43","doi-asserted-by":"crossref","DOI":"10.1016\/j.metabol.2022.155371","article-title":"Impaired hepatic glucose metabolism and liver-alpha-cell axis in mice with liver-specific ablation of the Hepatocyte Nuclear Factor 4alpha (Hnf4a) gene","volume":"139","author":"Thymiakou","year":"2023","journal-title":"Metabolism"},{"key":"10.1016\/j.molmet.2024.102075_bib44","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2022.110697","article-title":"HNF4A modulates glucocorticoid action in the liver","volume":"39","author":"Hunter","year":"2022","journal-title":"Cell Rep"},{"key":"10.1016\/j.molmet.2024.102075_bib45","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.2337\/diabetes.48.7.1459","article-title":"Functional characterization of the MODY1 gene mutations HNF4(R127W), HNF4(V255M), and HNF4(E276Q)","volume":"48","author":"Navas","year":"1999","journal-title":"Diabetes"},{"key":"10.1016\/j.molmet.2024.102075_bib46","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.isci.2019.05.032","article-title":"HNF4A haploinsufficiency in MODY1 abrogates liver and pancreas differentiation from patient-derived induced pluripotent stem cells","volume":"16","author":"Ng","year":"2019","journal-title":"iScience"},{"key":"10.1016\/j.molmet.2024.102075_bib47","doi-asserted-by":"crossref","DOI":"10.1093\/femsre\/fuaa061","article-title":"The PEP-pyruvate-oxaloacetate node: variation at the heart of metabolism","volume":"45","author":"Koendjbiharie","year":"2021","journal-title":"FEMS Microbiol Rev"}],"container-title":["Molecular Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2212877824002060?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2212877824002060?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T13:23:11Z","timestamp":1778851391000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2212877824002060"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1]]},"references-count":44,"alternative-id":["S2212877824002060"],"URL":"https:\/\/doi.org\/10.1016\/j.molmet.2024.102075","relation":{},"ISSN":["2212-8778"],"issn-type":[{"value":"2212-8778","type":"print"}],"subject":[],"published":{"date-parts":[[2025,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Leupaxin promotes hepatic gluconeogenesis and glucose metabolism by coactivation with hepatic nuclear factor 4\u03b1","name":"articletitle","label":"Article Title"},{"value":"Molecular Metabolism","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.molmet.2024.102075","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 The Author(s). Published by Elsevier GmbH.","name":"copyright","label":"Copyright"}],"article-number":"102075"}}