Carbohydrate-response-element-binding protein (ChREBP) and not the liver X receptor α (LXRα) mediates elevated hepatic lipogenic gene expression in a mouse model of glycogen storage disease type 1
| العنوان: | Carbohydrate-response-element-binding protein (ChREBP) and not the liver X receptor α (LXRα) mediates elevated hepatic lipogenic gene expression in a mouse model of glycogen storage disease type 1 |
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| المؤلفون: | Marijke Schreurs, Víctor Cortés, Dirk-Jan Reijngoud, Albert K. Groen, Rick Havinga, Maaike H. Oosterveer, Andreas W. Herling, Folkert Kuipers, Aldo Grefhorst |
| المساهمون: | Academic Medical Center, Center for Liver, Digestive and Metabolic Diseases (CLDM), Lifestyle Medicine (LM) |
| المصدر: | Biochemical journal, 432(2), 249-254. Portland Press Ltd. Biochemical Journal, 432(2), 249-254. PORTLAND PRESS LTD |
| بيانات النشر: | PORTLAND PRESS LTD, 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Male, Pyridines, glycogen storage disease type 1 (GSD-1), Biochemistry, GLUCOSE, chemistry.chemical_compound, Glycogen storage disease, TRANSCRIPTION, Liver X Receptors, Regulation of gene expression, Mice, Knockout, INSULIN-RESISTANCE, biology, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, CHOLESTEROL, liver X receptor (LXR), Imidazoles, Nuclear Proteins, Glycogen Storage Disease, Orphan Nuclear Receptors, sterol-regulatory element-binding protein-1c (SREBP-1c), Liver, pentose-5-phosphate pathway, Lipogenesis, Glucose 6-phosphatase, medicine.medical_specialty, METABOLISM, NUCLEAR RECEPTOR, Internal medicine, medicine, Animals, Humans, STEATOSIS, Carbohydrate-responsive element-binding protein, Liver X receptor, Molecular Biology, Triglycerides, glucose 6-phosphate, Cell Biology, medicine.disease, Sterol regulatory element-binding protein, Liver Glycogen, Mice, Inbred C57BL, carbohydrate-response-element-binding protein (ChREBP), Disease Models, Animal, MICE, GLUCOSE-6-PHOSPHATASE, Endocrinology, Glucose 6-phosphate, chemistry, Gene Expression Regulation, biology.protein, RNA, ACUTE INHIBITION, Transcription Factors |
| الوصف: | GSD-1 (glycogen storage disease type 1) 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 similar to 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 alpha (liver X receptor alpha) and ChREBP (carbohydrate-response-element-binding protein). Treatment of Lxra(-/-) mice and Chrebp(-/-) mice with S4048 demonstrated that ChREBP, but not LXR alpha., 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 |
| اللغة: | English |
| تدمد: | 0264-6021 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d05e7cc86550363253c143aae2e291c9Test https://doi.org/10.1042/BJ20101225Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d05e7cc86550363253c143aae2e291c9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 02646021 |
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