{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T18:13:33Z","timestamp":1784052813252,"version":"3.55.0"},"reference-count":25,"publisher":"American Society for Clinical Investigation","issue":"14","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,15]]},"abstract":"<jats:p>Metabolic dysfunction\u2013associated steatohepatitis (MASH) affects 1.5%\u20136.5% of the global population, yet its mechanisms remain incompletely understood. Cholesterol overload is a key driver of MASH, suggesting that targeting cholesterol sensing may offer therapeutic benefits. In this issue, Deng et al. identified nuclear factor erythroid 2\u2013related factor 1 (NFE2L1) as a critical regulator linking cholesterol sensing to VLDL-mediated lipid export. Mechanistically, NFE2L1 interacts with insulin-induced gene 1 (INSIG1) and promotes its degradation in hepatocytes. This cholesterol-dependent NFE2L1-INSIG1 interaction sustains SREBP activation and VLDL secretion to maintain hepatic and systemic lipid homeostasis. Moreover, the study by Deng et al. indicates that hepatic NFE2L1 overexpression decreases INSIG1 abundance and ameliorates MASH progression, highlighting its therapeutic potential.<\/jats:p>","DOI":"10.1172\/jci206628","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T18:01:13Z","timestamp":1784052073000},"source":"Crossref","is-referenced-by-count":0,"title":["Targeting hepatic cholesterol sensing to tackle metabolic dysfunction\u2013associated steatohepatitis"],"prefix":"10.1172","volume":"136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2502-2586","authenticated-orcid":true,"given":"Mengwei","family":"Zang","sequence":"first","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies, Center for Healthy Aging, and"},{"name":"Department of Molecular Medicine, University of Texas Health San Antonio, San Antonio, Texas, USA."},{"name":"Geriatric Research, Education and Clinical Center, South Texas Veterans Health Care System, San Antonio, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6910-5933","authenticated-orcid":true,"given":"Yu","family":"Li","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30251"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1136\/egastro-2025-100196"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2022.100479"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/hep4.1801"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.03.010"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26604"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2017.91"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2011.12.017"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1172\/JCI20978"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2024.01.011"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-019-0190-7"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2011.03.009"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0067532"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.42.30028"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2024.101409"},{"issue":"14","key":"B16","article-title":"Cholesterol-responsive NFE2L1-INSIG1 interaction controls VLDL secretion and metabolic dysfunction\u2013associated steatohepatitis pathogenesis in mice","volume":"136","author":"Deng","year":"2026","journal-title":"J Clin Invest"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2022.101436"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-024-01398-z"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.10.003"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200422422"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1126\/science.1204265"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2024-333074"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2022.104392"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27883"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.09.016"}],"container-title":["Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jci.org\/articles\/view\/206628\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T18:02:25Z","timestamp":1784052145000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jci.org\/articles\/view\/206628"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,15]]},"references-count":25,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2026,6,2]]},"published-print":{"date-parts":[[2026,7,15]]}},"alternative-id":["10.1172\/JCI206628"],"URL":"https:\/\/doi.org\/10.1172\/jci206628","relation":{},"ISSN":["1558-8238"],"issn-type":[{"value":"1558-8238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,15]]},"article-number":"e206628"}}