Organization of Extracellular Matrix Components During Differentiation of Adipocytes in Long-Term Culture

Abstract

Scanning electron microscopy (SEM) observation showed that fully differentiated spherical adipocytes were embraced by a network of collagens and fibroblastic preadipocytes. The properties of both the collagen networks and the preadipocytes allow the adipocytes to be interconnected, forming a fat-cell cluster, which can anchor to the bottom of a culture dish. In this network structure, collagen fibrils and fibrillar bundles were closely arranged and stratified. We found that immunostained collagens appeared to form extracellular network structures, which can be observed by SEM. The extracellular network of fibronectin was the first to develop among the extracellular matrix (ECM) components, though it became degraded with the progress of adipocyte differentiation. The type I collagen network was the last to develop and remained well organized through the late stage of adipocyte differentiation. The extracellular networks of type III, V, and VI collagen developed by the mid-stage and remained in the late stage of adipocyte differentiation. The network structures of type IV collagen and laminin became degraded during the differentiation process and localized at the surface of spherical cells. In addition to these basement membrane components, types III, V, and VI collagens also showed pericellular spherical staining patterns. These results demonstrated that the constitution and distribution of the ECM are altered during adipocyte differentiation, suggesting that the organization of each ECM component into a suitable structure is a requirement for the differentiation and maintenance of unilocular adipocytes.

Adipocyte transdifferentiation and its molecular targets

“…This is accompanied by dramatic changes in the cytoskeleton and extracellular matrix component (ECM). Decrease in actin and tubulin expression as well as fibroblast expressed type-I and III procollagen are also seen in the early stage of differentiation (Cryer and Van, 1982;Kubo et al, 2000). There is also a dramatic decrease in preadipocyte factor-1 (pref1) expression as cells differentiate from preadipocytes to mature adipocytes (Hudak and Sul, 2013;Wang et al, 2006).…”

The role of adipose protein derived hydrogels in adipogenesis

“…Studies have shown that BM deposition, synthesis and remodeling are enhanced during adipogenesis and are essential for adipocyte maturation [8,9]. Differentiated adipocytes first degrade the BM and subsequently synthesize new BM components including collagen type IV, laminins and fibronectin [10,11]. The new BM influences the initiation and maintenance of adipogenesis and remodeling of adipose tissue.…”

Subcutaneous fat in normal and diseased states

“…These changes in cell shape are paralleled by dramatic changes in the level and type of cytoskeletal, extracellular matrix (ECM) and related components, such as actin, tubulin, fibronectin, and collagen. 26,171,172 Emerging evidence suggests that ECM components play an important role in the regulation of adipose tissue remodeling during adipocyte differentiation and are necessary for progression of the adipogenic program. [172][173][174] The ECM not only influences the integrity of the structural system that supports cells, but also influences, via cell-surface receptors, cell-cell and cell-matrix interactions with impact on differentiation and cell migration.…”

“…Fibronectin, for example, an important cytoskeletal component of the ECM during initial stages of adipogenesis, inhibits adipogenesis at later stages, in part, by down-regulating the expression of lipogenic genes. 171,175 Throughout adipocyte differentiation, ECM components are synthesized by preadipocytes and degraded at various stages of the process. 171 Decreases in actin and tubulin expression mark an early event and appear to precede overt changes in cell morphology, 176 whereas early increases in fibronectin expression and secretion lead to the formation of an extracellular network structure.…”