Abstract
The canonical Wnt signaling pathway is ubiquitous throughout the body and influences a diverse array of physiological processes. Following the initial discovery of the Wnt signaling pathway during wing development in Drosophila melanogaster, it is now widely appreciated that active Wnt signaling in mammals is necessary for the development and growth of various tissues involved in whole-body metabolism, such as brain, liver, pancreas, muscle, and adipose. Moreover, elegant gain- and loss-of-function studies have dissected the tissue-specific roles of various downstream effector molecules in the regulation of energy homeostasis. This review attempts to highlight and summarize the contributions of the Wnt signaling pathway and its downstream effectors on whole-body metabolism and their influence on the development of metabolic diseases, such as diabetes and obesity. A better understanding of the Wnt signaling pathway in these tissues may aid in guiding the development of future therapeutics to treat metabolic diseases.
Highlights
During embryogenesis, the Wnt signaling pathway has active and critical roles in tissue development, including, but not limited to, axon guidance, body segmentation, limb development, and stem cell differentiation (Yang, 2003; Dunty et al, 2008; Geetha-Loganathan et al, 2008; Nusse, 2008; Stanganello et al, 2019)
Some of the lesser appreciated functions of the Wnt signaling pathway are its influence on systemic, organ, and tissue metabolism and energy homeostasis
The liver is a critical metabolic tissue, as it is capable of glucose and glycogen metabolism, gluconeogenesis, fatty acid metabolism, and drug metabolism (Rui, 2014)
Summary
The Wnt signaling pathway has active and critical roles in tissue development, including, but not limited to, axon guidance, body segmentation, limb development, and stem cell differentiation (Yang, 2003; Dunty et al, 2008; Geetha-Loganathan et al, 2008; Nusse, 2008; Stanganello et al, 2019). Some of the lesser appreciated functions of the Wnt signaling pathway are its influence on systemic, organ, and tissue metabolism and energy homeostasis. Whole-body metabolism is regulated by various tissues, including brain, liver, pancreas, muscle and adipose, and each contributes significantly to carbohydrate and/or lipid metabolism. Skeletal muscles require glucose and fatty acids to function, and can themselves be metabolized and converted to amino acids for use by other tissues. Insulin promotes glucose uptake in muscle where it can be stored as glycogen (McPherron et al, 2013). Adipose tissue functions as energy reservoirs, and secretes key hormones and metabolites to help control systemic energy balance (Choe et al, 2016). The goal of this review is aimed at highlighting the important contributions of the Wnt signaling pathway and its effectors within these metabolic tissues
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