We have previously shown the SLRP decorin to be highly expressed in adipose tissue, and upregulated in obesity suggesting a potential role in adipose tissue homeostasis or in the pathophysiology associated with obesity such as extracellular matrix (ECM) remodeling, inflammation, and angiogenesis within expanding adipose tissue. Here we extend these findings to include the closely related SLRP, biglycan, which also exhibits high expression in adipose tissue (and particularly visceral adipose tissue) compared to a wide variety of tissues examined, and increased expression in obesity.
Collectively, these data raise the possibility that increased expression of SLRPs in adipose tissue is a key feature during the development of obesity, T2D, and the metabolic syndrome. SLRPs are constituents of the ECM which undergoes constant degradation and renewal,15
allows the diffusion of nutrients, metabolites, and hormones between blood and cells within the tissue16
and functions not only as a scaffold for cells within tissues, but also as a reservoir of growth factors and cytokines and modulates their activities.17
SLRPs bind and interact with numerous proteins involved in matrix assembly, cell proliferation, and tissue morphogenesis. 18
With regards to adipocyte differentiation, remarkable changes in cell morphology, cytoskeletal components, and the amount and type of ECM components secreted occurs.19
Furthermore, the development of obesity requires extensive reorganization of adipose tissue and the expression of genes involved in matrix remodeling was found to be increased in obese db/db mice and resulted in the net accumulation of ECM components in parallel to increased adipocyte size.20
It has also been proposed that complications of diabetes are closely associated with changes in the ECM21
as macroangiopathic and microangiopathic complications resultant from the presence of diabetes have involved abnormalities within the extracellular intima.21
Given the above background information regarding SLRPs, it is therefore tempting to speculate that SLRPs may play a role in angiogenesis and ECM remodeling within expanding adipose tissue during the development of obesity and T2D. Recent studies have demonstrated biglycan
to be upregulated in a murine model of diet-induced obesity with atherosclerosis,23
to be involved in vascular and proatherogenic remodeling in a rat model of metabolic syndrome,24
to be proangiogenic,25
and interestingly, to have upregulated expression in parallel with matrix degradation genes in white adipose tissue from db/db mice fed a high fat diet.20
has also been demonstrated to be upregulated in human omental compared to lean adipose tissue.26
This evidence builds upon the hypothesized role for biglycan
in adipose tissue homeostasis, particularly in states of obesity where ECM remodeling is required for adipose tissue expansion.
has been shown to be proinflammatory and acts through toll-like receptors in macrophages.27
Recent studies have supported a strong association of biglycan
with inflammation, demonstrating increased levels of tumor necrosis factor α
(a major inflammatory cytokine implicated in T2D) and biglycan
in human omental adipose tissue, suggesting they may be coregulated.26
This potentially associates biglycan
to obesity which is associated with a chronic low grade inflammatory state in adipose tissue (particularly visceral adipose tissue),30
and the subsequent development of insulin resistance and T2D.30
However, these are postulated theories, therefore additional experiments to explore a role in inflammation and substantiate these theories are now required.
In summary, our data suggest that the family of SLRPs may play a role in the development of obesity and T2D, with a hypothesized role of facilitating the expansion of adipose tissue mass within an animal model. Further work is now required to corroborate these results within humans.