Crucial Roles of Glycosaminoglycans in Systemic Energy Homeostasis

Glycosaminoglycans (GAGs), which are present on the cell surface and in the extracellular matrix, are critical regulatory factors that modulate signal transduction through interactions with bioactive molecules and maintain tissue homeostasis. This review highlights the roles of GAGs, particularly heparan sulfate (HS), in energy homeostasis, with a primary focus on adipose tissue, while also covering their functions in pancreatic β cells, vascular endothelium, and the liver. HS regulates fibroblast growth factor and insulin signaling, contributing to adipocyte differentiation, metabolic flexibility, and the maintenance of glucose and lipid homeostasis. Furthermore, aberrant structural modifications of HS may contribute to a positive feedback loop that exacerbates chronic inflammation and insulin resistance.