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| Status |
Public on Nov 01, 2012 |
| Title |
Diabetes risk gene and Wnt effector Tcf7l2/TCF4 controls hepatic response to perinatal and adult metabolic demand |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
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 β-cells. Here, a mouse genetics approach shows that removal of TCF4 from β-cells does not affect their function, while 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. 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.
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| Overall design |
RNA was extracted from liver tissues of the Tcf7l2 wildtype or knockout mice with treatments as indicated. Microarray analysis was performed to compare the expression profile changes between Tcf7l2 knockout and wildtype mice in response to treatment.
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| Contributor(s) |
Boj SF, Li VS, Clevers H |
| Citation(s) |
23260145 |
| |
| Submission date |
Oct 02, 2012 |
| Last update date |
May 10, 2018 |
| Contact name |
Vivian Li |
| E-mail(s) |
vivian.li@crick.ac.uk
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| Organization name |
The Francis Crick Institute
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| Lab |
Stem Cell and Cancer Biology
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| Street address |
1 Midland Road
|
| City |
London |
| ZIP/Postal code |
NW1 1AT |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL4134 |
Agilent-014868 Whole Mouse Genome Microarray 4x44K G4122F (Feature Number version) |
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| Samples (22)
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| Relations |
| BioProject |
PRJNA176444 |
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