Wnt signaling pathway – its role in regulation of cell metabolism

Abstract

The Wnt signaling pathway plays an important role in morphogenesis, differentiation, cell survival and proliferation. Wnt activators are secreted proteins that work in an auto-, para- and endocrine manner and their synthesis, secretion and transport are tightly regulated. Frizzled/LRP is the main receptor complex in the canonical Wnt pathway. Its activation triggers β-catenin translocation to the nucleus and increases activity of TCF transcription factor. Disruption in Wnt signaling has been found in many pathophysiological states such as different types of cancer, neurodegenerative diseases and metabolic disorders. Recent studies revealed the important role of Wnt signaling in maintaining carbohydrate and lipid homeostasis. Activation of the Frizzled/LRP receptor complex leads to increase in the activity of transcription factors and nuclear receptors that regulate expression of genes involved in lipid utilization (PPARδ, RAR, LXR) and inhibits adipogenesis. The Wnt signaling pathway is also involved in the regulation of gluconeogenesis and glycolysis. This review summarizes the current state of knowledge about mechanisms that regulate canonical Wnt signaling and its role in cell metabolism regulation.