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Extracellular Matrix Remodeling
and Mechanical Stresses as Modulators
of Adipose Tissue Metabolism
and Inflammation
Kyongbum Lee and Catherine K. Kuo
Abstract 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, inflam-
mation, 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 con-
straining 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 mech-
anotransduction 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
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