| First Author | Liu H | Year | 2011 |
| Journal | Sci Signal | Volume | 4 |
| Issue | 158 | Pages | ra6 |
| PubMed ID | 21285411 | Mgi Jnum | J:185396 |
| Mgi Id | MGI:5428391 | Doi | 10.1126/scisignal.2001249 |
| Citation | Liu H, et al. (2011) Wnt signaling regulates hepatic metabolism. Sci Signal 4(158):ra6 |
| abstractText | The contribution of the Wnt pathway has been extensively characterized in embryogenesis, differentiation, and stem cell biology but not in mammalian metabolism. Here, using in vivo gain- and loss-of-function models, we demonstrate an important role for Wnt signaling in hepatic metabolism. In particular, beta-catenin, the downstream mediator of canonical Wnt signaling, altered serum glucose concentrations and regulated hepatic glucose production. beta-Catenin also modulated hepatic insulin signaling. Furthermore, beta-catenin interacted with the transcription factor FoxO1 in livers from mice under starved conditions. The interaction of FoxO1 with beta-catenin regulated the transcriptional activation of the genes encoding glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK), the two rate-limiting enzymes in hepatic gluconeogenesis. Moreover, starvation induced the hepatic expression of mRNAs encoding different Wnt isoforms. In addition, nutrient deprivation appeared to favor the association of beta-catenin with FoxO family members, rather than with members of the T cell factor of transcriptional activators. Notably, in a model of diet-induced obesity, hepatic deletion of beta-catenin improved overall metabolic homeostasis. These observations implicate Wnt signaling in the modulation of hepatic metabolism and raise the possibility that Wnt signaling may play a similar role in the metabolic regulation of other tissues. |
