Wnt Signaling: From Mesenchymal Cell Fate to Lipogenesis and Other Mature Adipocyte Functions.

Wnt signaling is an ancient and evolutionarily conserved pathway with fundamental roles in the development of adipose tissues. Roles of this pathway in mesenchymal stem cell fate determination and differentiation have been extensively studied. Indeed, canonical Wnt signaling is a significant endogenous inhibitor of adipogenesis and promoter of other cell fates, including osteogenesis, chondrogenesis, and myogenesis. However, emerging genetic evidence in both humans and mice suggests central roles for Wnt signaling in body fat distribution, obesity, and metabolic dysfunction. Herein, we highlight recent studies that have begun to unravel the contributions of various Wnt pathway members to critical adipocyte functions, including carbohydrate and lipid metabolism. We further explore compelling evidence of complex and coordinated interactions between adipocytes and other cell types within adipose tissues, including stromal, immune, and endothelial cells. Given the evolutionary conservation and ubiquitous cellular distribution of this pathway, uncovering the contributions of Wnt signaling to cell metabolism has exciting implications for therapeutic intervention in widespread pathologic states, including obesity, diabetes, and cancers.