{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T15:10:48Z","timestamp":1792422648562,"version":"4.5.0"},"reference-count":42,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T00:00:00Z","timestamp":1749168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Science and innovation","doi-asserted-by":"publisher","award":["PI20\/01806"],"award-info":[{"award-number":["PI20\/01806"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Science and innovation","doi-asserted-by":"publisher","award":["PI21\/00462"],"award-info":[{"award-number":["PI21\/00462"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Science and innovation","doi-asserted-by":"publisher","award":["PMP22\/00073"],"award-info":[{"award-number":["PMP22\/00073"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Science and innovation","doi-asserted-by":"publisher","award":["PI24\/\/00852"],"award-info":[{"award-number":["PI24\/\/00852"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Regional development Fund (ERDF)","award":["PI20\/01806"],"award-info":[{"award-number":["PI20\/01806"]}]},{"name":"European Regional development Fund (ERDF)","award":["PI21\/00462"],"award-info":[{"award-number":["PI21\/00462"]}]},{"name":"European Regional development Fund (ERDF)","award":["PMP22\/00073"],"award-info":[{"award-number":["PMP22\/00073"]}]},{"name":"European Regional development Fund (ERDF)","award":["PI24\/\/00852"],"award-info":[{"award-number":["PI24\/\/00852"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Zinc-alpha2-glycoprotein (ZAG) is a soluble glycoprotein primarily produced in adipocytes and the liver, with key roles in lipid metabolism, including lipolysis and the browning of adipose tissue. Despite extensive studies on its role in rodents, the relationship between ZAG and insulin in humans remains unclear. Given the emerging interest in ZAG\u2019s involvement in metabolic diseases such as metabolic-dysfunction-associated steatotic liver disease, this study aimed to investigate the acute effects of insulin on ZAG levels both in vivo and in vitro. We recruited 24 healthy, individuals who were non-obese and assessed the impact of oral glucose overload, a standardized liquid nutritional supplement, and intravenous glucagon on circulating ZAG levels. In parallel, we explored the effects of insulin on ZAG production in cultured HepG2 cells. Our findings revealed a consistent acute reduction in serum ZAG levels following all in vivo tests, coinciding with increased insulin levels. In vitro, insulin rapidly downregulated ZAG protein and mRNA levels in HepG2 cells, with significant reductions observed within 15 min, followed by partial recovery after 2 h. These results suggest a potential acute inhibitory effect of insulin on ZAG production, supporting its role in promoting energy storage by suppressing lipolysis postprandially. This study provides new insights into the complex interplay between insulin and ZAG in regulating energy balance and highlights the potential of ZAG as a therapeutic target in metabolic diseases.<\/jats:p>","DOI":"10.3390\/ijms26125438","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T06:11:08Z","timestamp":1749190268000},"page":"5438","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Acute Downregulation of Zinc \u03b12-Glycoprotein: Evidence from Human and HepG2 Cell Studies"],"prefix":"10.3390","volume":"26","author":[{"given":"\u00c8lia","family":"Navarro-Masip","sequence":"first","affiliation":[{"name":"Obesity, Diabetes and Metabolism (ODIM) Research Group, Lleida Biomedical Research Institute (IRBLLeida), University of Lleida, 25198 Lleida, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Selva","sequence":"additional","affiliation":[{"name":"Diabetes and Metabolism Research Unit, Institut de Recerca Hospital Universitari Vall d\u2019Hebron, Universitat Aut\u00f2noma de Barcelona, 08035 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n en Red en Diabetes y Enfermedades Metab\u00f3licas (CIBERdem), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3109-1721","authenticated-orcid":false,"given":"Cristina","family":"Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Diabetes and Metabolism Research Unit, Institut de Recerca Hospital Universitari Vall d\u2019Hebron, Universitat Aut\u00f2noma de Barcelona, 08035 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n en Red en Diabetes y Enfermedades Metab\u00f3licas (CIBERdem), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5622-0203","authenticated-orcid":false,"given":"Andreea","family":"Ciudin","sequence":"additional","affiliation":[{"name":"Diabetes and Metabolism Research Unit, Institut de Recerca Hospital Universitari Vall d\u2019Hebron, Universitat Aut\u00f2noma de Barcelona, 08035 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n en Red en Diabetes y Enfermedades Metab\u00f3licas (CIBERdem), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1668-7594","authenticated-orcid":false,"given":"Blanca","family":"Salinas-Roca","sequence":"additional","affiliation":[{"name":"Obesity, Diabetes and Metabolism (ODIM) Research Group, Lleida Biomedical Research Institute (IRBLLeida), University of Lleida, 25198 Lleida, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Cabrera-Serra","sequence":"additional","affiliation":[{"name":"Diabetes and Metabolism Research Unit, Institut de Recerca Hospital Universitari Vall d\u2019Hebron, Universitat Aut\u00f2noma de Barcelona, 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0475-3096","authenticated-orcid":false,"given":"Rafael","family":"Sim\u00f3","sequence":"additional","affiliation":[{"name":"Diabetes and Metabolism Research Unit, Institut de Recerca Hospital Universitari Vall d\u2019Hebron, Universitat Aut\u00f2noma de Barcelona, 08035 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n en Red en Diabetes y Enfermedades Metab\u00f3licas (CIBERdem), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Lecube","sequence":"additional","affiliation":[{"name":"Diabetes and Metabolism Research Unit, Institut de Recerca Hospital Universitari Vall d\u2019Hebron, Universitat Aut\u00f2noma de Barcelona, 08035 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n en Red en Diabetes y Enfermedades Metab\u00f3licas (CIBERdem), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.1126\/science.283.5409.1914","article-title":"Crystal structure of human ZAG, a fat-depleting factor related to MHC molecules","volume":"283","author":"Chirino","year":"1999","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1177\/39.9.1918940","article-title":"Immunohistochemical localization of Zn-\u03b12-glycoprotein in normal human tissues","volume":"39","author":"Tada","year":"1991","journal-title":"J. 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