Adipose Tissue Extracellular Matrix Remodeling: A Driver of Obesity and Insulin Resistance

This review explores the role of extracellular matrix (ECM) in adipose tissue highlighting its composition, regulation, and impact on obesity and insulin resistance. The ECM in adipocytes is a dynamic entity and highly organized network composed of structural proteins which provide mechanical support for cells and tissues and regulate cellular signaling. ECM modifiers, such as matrix metalloproteinases and tissue inhibitors of metalloproteinases, coordinate ECM remodeling to allow the expansion of adipocytes. Furthermore, ECM receptors like integrins and CD44 mediate adipocytes-microenvironment interactions, affecting the inflammatory process resulting in insulin resistance. The ECM components are posttranslational being modified by an array of remodeling enzymes, such as lysyl oxidase and prolyl-4-hydroxylase, to regulate ECM integrity. While excessive ECM deposition and fibrosis urge physical constraints on adipocyte expansion, ECM remodeling emerges as a denominator linking obesity and insulin resistance associated with vascular dysfunction and severe inflammation emphasizing the role of ECM in metabolic diseases.