Research ArticleMetabolism

Wnt Signaling Regulates Hepatic Metabolism

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Science Signaling  01 Feb 2011:
Vol. 4, Issue 158, pp. ra6
DOI: 10.1126/scisignal.2001249

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β-Catenin for Gluconeogenesis

In the canonical Wnt signaling pathway, binding of Wnt ligands to receptors stabilizes β-catenin, leading to the initiation of gene transcription by β-catenin in the nucleus. The role of the Wnt signaling pathway has been well established in developmental processes; however, growing evidence also implicates this pathway in the regulation of metabolism. Liu et al. found that hepatic deletion of β-catenin in mice decreased gluconeogenesis (the process by which the liver produces glucose) and serum glucose concentrations. More β-catenin interacted with the transcription factor FoxO1 (which is involved in transcriptional responses to insulin signaling) in hepatocytes from starved compared to fed mice, an interaction that promoted the transcriptional activation of genes encoding gluconeogenic enzymes. In obese mice, hepatic deletion of β-catenin improved overall glucose tolerance and reduced hepatic gluconeogenesis. Thus, therapies that target β-catenin function in the liver could be used to treat metabolic diseases such as diabetes.