Characteristic Expression of Extracellular Matrix in Subcutaneous Adipose Tissue Development and Adipogenesis; Comparison with Visceral Adipose Tissue

Abstract

Adipose tissue is a connective tissue specified for energy metabolism and endocrines, but functional differences between subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) have not been fully elucidated. To reveal the physiological role of SAT, we characterized in vivo tissue development and in vitro adipocyte differentiation. In a DNA microarray analysis of SAT and VAT in Wistar rats, functional annotation clusters of extracellular matrix (ECM)-related genes were found in SAT, and major ECM molecules expressed in adipose tissues were profiled. In a histological analysis and quantitative expression analysis, ECM expression patterns could be classified into two types: (i) a histogenesis-correlated type such as type IV and XV collagen, and laminin subunits, (ii) a high-SAT expression type such as type I, III, and V collagen and minor characteristic collagens. Type (i) was related to basal membrane and up-regulated in differentiated 3T3-L1 cells and in histogenesis at depot-specific timings. In contrast, type (ii) was related to fibrous forming and highly expressed in 3T3-L1 preadipocytes. Exceptionally, fibronectin was abundant in developed adipose tissue, although it was highly expressed in 3T3-L1 preadipocytes. The present study showed that adipose tissues site-specifically regulate molecular type and timing of ECM expression, and suggests that these characteristic ECM molecules provide a critical microenvironment, which may affect bioactivity of adipocyte itself and interacts with other tissues. It must be important to consider the depot-specific property for the treatment of obesity-related disorders, dermal dysfunction and for the tissue regeneration.

The miR-181d-regulated metalloproteinase Adamts1 enzymatically impairs adipogenesis via ECM remodeling

“…In addition, Adamts1 also catalyzes the degradation of typical fibril-forming collagens such as Col1α1 and Col5α1, which have been defined as a 'high-iWAT expression type'. 10 Moreover, the expression level of these ECM proteins were positively correlated with obesity, which further support a functional role of Adamts1 during adipogenesis (Supplementary Figure S3). It should be noted that the regulation of ECM is a complex systematic process involving a large number of molecules.…”

“…In addition, adipogenesis was also restored (Figures 3d and e; Supplementary Figure S3A and B). To explore Adamts1 substrates impacting adipocyte lineage commitment, expression of the ECM proteins Thbs1, Fibronectin, and collagens 5,[8][9][10] were evaluated. These molecules were downregulated by Adamts1 overexpression with/out BMP4, but not by Adamts1 enzyme inactivation (Figure 3f).…”

“…4,10,38 The function of adipose tissue is regulated by physiological interactions between cells and ECM miR-181d-regulated Adamts1 impairs adipogenesis S-Z Chen et al proteins. 4,39,40 Adipocyte differentiation requires space expansion, which stems from ECM remodeling.…”

“…9 Fibronectin is also abundant in mature adipose tissue. 10 Moreover, other matrix components such as SPARC, osteopontin, decorin, and tenascin C increase significantly in white adipose tissue of obesity individuals. [11][12][13] These reports suggest that common ECM molecules provide a critical microenvironment that may impact adipocyte bioactivity and interaction with other cell types.…”

Adipose tissue macrophages in non-rodent mammals: a comparative study

“…Sections were cut with a Leica cryostat at a chamber temperature of −25°C. Cryosectioned specimens were used for the immunostaining of the lysosome protein Mac-3/Lamp-2 or laminin, which is a marker of the extracellular matrix of adipose tissue (Mori et al 2014). Sections were covered with 0.1 % Triton-X 100 containing PBS and then incubated with 2 % normal goat serum for 1 h. After being washed with PBS, the samples were incubated overnight with a rat antibody raised against mouse Mac-3/Lamp-2 (sc 19991, Santa Cruz) or laminin (ab11575, AbCam).…”