| First Author | Grefhorst A | Year | 2010 |
| Journal | Biochem J | Volume | 432 |
| Issue | 2 | Pages | 249-54 |
| PubMed ID | 20854262 | Mgi Jnum | J:167019 |
| Mgi Id | MGI:4866984 | Doi | 10.1042/BJ20101225 |
| Citation | Grefhorst A, et al. (2010) Carbohydrate-response-element-binding protein (ChREBP) and not the liver X receptor alpha (LXRalpha) mediates elevated hepatic lipogenic gene expression in a mouse model of glycogen storage disease type 1. Biochem J 432(2):249-54 |
| abstractText | 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 ~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, LXRalpha (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 LXRalpha, 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. |
