Extracellular Matrix Remodeling and Mechanical Stresses as Modulators of Adipose Tissue Metabolism and Inflammation

Adipose tissue depots experience a variety of physical stresses in the body. There is increasing evidence that these stresses elicit specific biological responses, and could play important roles in both physiological and pathological processes. In this chapter, we review recent studies investigating the potential mechanical influences arising from interactions between adipose cells and their extracellular matrix (ECM). We focus on cell–ECM interactions that govern adipocyte differentiation and maturation as well as those that could develop as adipocytes increase in size to store triglycerides in response to a positive energy balance. Hypertrophic enlargement of adipocytes often precedes fibrosis, inflammation, and metabolic alterations associated with an obese phenotype such as insulin resistance and hyperlipidemia. These changes in adipose tissue structure and function could be related via mechanisms involving mechanotransduction. Deposition of excess collagen fibers could stiffen the tissue, physically constraining the expandability of adipocytes. Additionally, cells may experience mechanical influences resulting from body movements. All of these could result in increased compression and/or tension on the adipocyte cellular membrane. Compelling in vitro data suggest that these stresses can activate classical mechanotransduction pathways in adipocytes and their precursor cells, notably the Rho-associated protein kinase (ROCK). Despite progress, many challenges remain in addressing mechanistic questions regarding the role of physiologically relevant mechanical influences in isolation from confounding biochemical influences present in vivo. In this regard, we expect engineered ECM and advanced bioreactors to serve as valuable model systems to dissect the effects of mechanical stresses under controlled chemical conditions.