Role and Regulation of Wnt/β-Catenin in Hepatic Perivenous Zonation and Physiological Homeostasis

Abstract

Metabolic heterogeneity or functional zonation is a key characteristic of the liver that allows different metabolic pathways to be spatially regulated within the hepatic system and together contribute to whole body homeostasis. These metabolic pathways are segregated along the portocentral axis of the liver lobule into three hepatic zones: periportal, intermediate or midzonal, and perivenous. The liver performs complementary or opposing metabolic functions within different hepatic zones while synergistic functions are regulated by overlapping zones, thereby maintaining the overall physiological stability. The Wnt/β-catenin signaling pathway is well known for its role in liver growth, development, and regeneration. In addition, the Wnt/β-catenin pathway plays a fundamental and dominant role in hepatic zonation and signals to orchestrate various functions of liver metabolism and pathophysiology. The β-catenin protein is the central player in the Wnt/β-catenin signaling cascade, and its activation is crucial for metabolic patterning of the liver. However, dysregulation of Wnt/β-catenin signaling is also implicated in different liver pathologies, including those associated with metabolic syndrome. β-Catenin is preferentially localized in the central region of the hepatic lobule surrounding the central vein and regulates multiple functions of this region. This review outlines the role of Wnt/β-catenin signaling pathway in controlling the different metabolic processes surrounding the central vein and its relation to liver homeostasis and dysfunction.