Adipose tissue is a highly plastic organ whose remodeling dynamics are central to whole-body metabolic health. Expansion of white adipose tissue occurs through either hyperplasia, which preserves tissue function, or hypertrophy, which causes local hypoxia, inflammation, and pathological extracellular matrix (ECM) accumulation. Under hypertrophic conditions, the ECM stiffens and transitions from a supportive scaffold to a fibrotic barrier that limits expansion and perpetuates metabolic dysfunction. Understanding how mechanical cues regulate adipose tissue remodeling is, therefore, essential for identifying new therapeutic strategies. Two mechanosensitive cell populations, adipose stem cells (ASC) and mature adipocytes, are central to this process. ASC interpret ECM stiffness and compositional changes, which determine lineage outcomes. Soft and flexible matrices favor adipogenesis, whereas stiff matrices drive fibroblast-like activation and matrix deposition. Adipocytes, though differentiated, retain mechanosensitive signaling capabilities that shape their function. Under chronic mechanical stresses, cytoskeletal remodeling pathways lead to changes in gene expression and partial dedifferentiation toward a fibroblast-like phenotype. Reciprocal signaling between ASC and adipocytes amplifies these processes, establishing feedback loops that reinforce either healthy or pathological remodeling. Cell and tissue engineering approaches are essential for dissecting these processes, with hydrogel substrates, 3D scaffolds, compression assays, and atomic force microscopy offering physiologically relevant platforms to model progenitors and adipose tissue cellular mechanics. Emerging tools, including nanotopography and mechanical stimulation devices, have the capacity to further clarify how mechanical signals influence adipose remodeling. By positioning ASC and adipocytes as active regulators of ECM mechanics, we underscore the importance of mechanotransduction pathways in adipose tissue health and point to bioengineering strategies that may help discover ways to restore tissue flexibility and improve metabolic outcomes.
Impact Statement
Adipose tissue function is dependent on its ability to remodel in response to metabolic demands. Mechanical cues from the extracellular matrix (ECM) dictate whether remodeling under conditions of obesity proceeds via adaptive hyperplasia or maladaptive fibrosis. This review highlights how adipose stem cells and mature adipocytes integrate ECM mechanics through integrin signaling, cytoskeletal remodeling, and mechanosensitive transcriptional pathways. By connecting mechanobiology to adipose tissue health, we emphasize both the fundamental biology and engineering approaches of targeting mechanical signaling to restore adipose tissue plasticity and improve systemic metabolic health.
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