| First Author | Boj SF | Year | 2012 |
| Journal | Cell | Volume | 151 |
| Issue | 7 | Pages | 1595-607 |
| PubMed ID | 23260145 | Mgi Jnum | J:193325 |
| Mgi Id | MGI:5468191 | Doi | 10.1016/j.cell.2012.10.053 |
| Citation | Boj SF, et al. (2012) Diabetes risk gene and Wnt effector Tcf7l2/TCF4 controls hepatic response to perinatal and adult metabolic demand. Cell 151(7):1595-607 |
| abstractText | Most studies on TCF7L2 SNP variants in the pathogenesis of type 2 diabetes (T2D) focus on a role of the encoded transcription factor TCF4 in beta cells. Here, a mouse genetics approach shows that removal of TCF4 from beta cells does not affect their function, whereas manipulating TCF4 levels in the liver has major effects on metabolism. In Tcf7l2(-/-) mice, the immediate postnatal surge in liver metabolism does not occur. Consequently, pups die due to hypoglycemia. By combining chromatin immunoprecipitation with gene expression profiling, we identify a TCF4-controlled metabolic gene program that is acutely activated in the postnatal liver. In concordance, adult liver-specific Tcf7l2 knockout mice show reduced hepatic glucose production during fasting and display improved glucose homeostasis when maintained on high-fat diet. Furthermore, liver-specific TCF4 overexpression increases hepatic glucose production. These observations imply that TCF4 directly activates metabolic genes and that inhibition of Wnt signaling may be beneficial in metabolic disease. |
