Abstract

Obesity promotes increased secretion of a number of inflammatory factors from adipose tissue. These factors include cytokines and very lately, extracellular matrix components (ECM). Biglycan, a small leucine rich proteoglycan ECM protein, is up-regulated in obesity and has recently been recognized as a pro-inflammatory molecule. However, it is unknown whether biglycan contributes to adipose tissue dysfunction. In the present study, we characterized biglycan expression in various adipose depots in wild-type mice fed a low fat diet (LFD) or obesity-inducing high fat diet (HFD). High fat feeding induced biglycan mRNA expression in multiple adipose depots. Adiponectin is an adipokine with anti-inflammatory and insulin sensitizing effects. Due to the importance of adiponectin, we examined the effect of biglycan on adiponectin expression. Comparison of adiponectin expression in biglycan knockout (bgn−/0) and wild-type (bgn+/0) reveals higher adiponectin mRNA and protein in epididymal white adipose tissue in bgn−/0 mice, as well higher serum concentration of adiponectin, and lower serum insulin concentration. On the contrary, knockdown of biglycan in 3T3-L1 adipocytes led to decreased expression and secretion of adiponectin. Furthermore, treatment of 3T3-L1 adipocytes with conditioned medium from biglycan treated macrophages resulted in an increase in adiponectin mRNA expression. These data suggest a link between biglycan and adiponectin expression. However, the difference in the pattern of regulation between in vivo and in vitro settings reveals the complexity of this relationship.

Highlights

  • Biglycan is a class I member of the small leucine rich proteoglycan (SLRP) family [1] and a component of the extracellular matrix (ECM)

  • Immunohistochemistry was performed to determine the distribution of biglycan in epididymal white adipose tissue (EWAT) under low fat diet (LFD) and high fat diet (HFD) bgn+/0 mice

  • To determine which cells within the adipose tissue are contributing to biglycan content, we measured biglycan transcript levels in primary adipocytes and stromal vascular cells (SVC) from EWAT of HFD fed wild-type mice

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Summary

Introduction

Biglycan is a class I member of the small leucine rich proteoglycan (SLRP) family [1] and a component of the extracellular matrix (ECM). Biglycan is associated with bone formation, collagen interaction, and TGF-b signaling [2,3,4]. Multiple studies show that biglycan is present in the adipose tissue and adipocytes [7,8,9,10]. Biglycan is expressed in mouse adipose tissue [7,8], and proteomic and genomic profiling studies show that biglycan gene expression is modulated during adipogenesis, with evidence for increased expression in human mesenchymal stem cells [9] and 3T3-L1 [10] adipocytes. Proteomic analysis indicates reduced biglycan protein level during adipocyte differentiation [11]. At present it is still unknown whether biglycan contributes to adipose tissue dysfunction in obesity

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