{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T08:46:47Z","timestamp":1791103607046,"version":"4.1.0"},"reference-count":39,"publisher":"Portland Press Ltd.","issue":"2","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,12,1]]},"abstract":"<jats:p>GSD-1 (glycogen storage disease type\u00a01) is caused by an inherited defect in glucose-6-phosphatase activity, resulting in a massive accumulation of hepatic glycogen content and an induction of de novo lipogenesis. The chlorogenic acid derivative S4048 is a pharmacological inhibitor of the glucose 6-phosphate transporter, which is part of glucose-6-phosphatase, and allows for mechanistic studies concerning metabolic defects in GSD-1. Treatment of mice with S4048 resulted in an ~60% reduction in blood glucose, increased hepatic glycogen and triacylglycerol (triglyceride) content, and a markedly enhanced hepatic lipogenic gene expression. In mammals, hepatic expression of lipogenic genes is regulated by the co-ordinated action of the transcription factors SREBP (sterol-regulatory-element-binding protein)-1c, LXR\u03b1 (liver X receptor \u03b1) and ChREBP (carbohydrate-response-element-binding protein). Treatment of Lxra\u2212\/\u2212 mice and Chrebp\u2212\/\u2212 mice with S4048 demonstrated that ChREBP, but not LXR\u03b1, mediates the induction of hepatic lipogenic gene expression in this murine model of GSD-1. Thus ChREBP is an attractive target to alleviate derangements in lipid metabolism observed in patients with GSD-1.<\/jats:p>","DOI":"10.1042\/bj20101225","type":"journal-article","created":{"date-parts":[[2010,9,21]],"date-time":"2010-09-21T08:29:51Z","timestamp":1285057791000},"page":"249-254","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Carbohydrate-response-element-binding protein (ChREBP) and not the liver X receptor \u03b1 (LXR\u03b1) mediates elevated hepatic lipogenic gene expression in a mouse model of glycogen storage disease type\u00a01"],"prefix":"10.1042","volume":"432","author":[{"given":"Aldo","family":"Grefhorst","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marijke","family":"Schreurs","sequence":"additional","affiliation":[{"name":"Molecular Genetics Section, Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maaike\u00a0H.","family":"Oosterveer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor\u00a0A.","family":"Cort\u00e9s","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rick","family":"Havinga","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas\u00a0W.","family":"Herling","sequence":"additional","affiliation":[{"name":"Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk-Jan","family":"Reijngoud","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert\u00a0K.","family":"Groen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"},{"name":"Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Folkert","family":"Kuipers","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"},{"name":"Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2010,11,12]]},"reference":[{"key":"2021112217341800000_B1","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1067\/mpd.2002.121382","article-title":"Increased lipogenesis and resistance of lipoproteins to oxidative modification in two patients with glycogen storage disease type\u00a0Ia","volume":"140","author":"Bandsma","year":"2002","journal-title":"J. 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