Enhanced biglycan gene expression in the adipose tissues of obese women and its association with obesity-related genes and metabolic parameters.

Jimin Kim,Joon Pio Hong,Gyung-Yub Gong,Yoon-Suk Heo,Ji-Min Shin,Un-Woo Jeoun,Hye Soon Park,Seul Ki Lee,Yeon Ji Lee,Jong-Hyeok Kim,Yeon Jin Jang,Taik Jong Lee

doi:10.1038/srep30609

Jimin Kim, Joon Pio Hong + Show 10 more

Open Access

https://doi.org/10.1038/srep30609

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Abstract

Extracellular matrix (ECM) remodeling dynamically occurs to accommodate adipose tissue expansion during obesity. One non-fibrillar component of ECM, biglycan, is released from the matrix in response to tissue stress; the soluble form of biglycan binds to toll-like receptor 2/4 on macrophages, causing proinflammatory cytokine secretion. To investigate the pattern and regulatory properties of biglycan expression in human adipose tissues in the context of obesity and its related diseases, we recruited 21 non-diabetic obese women, 11 type 2 diabetic obese women, and 59 normal-weight women. Regardless of the presence of diabetes, obese patients had significantly higher biglycan mRNA in both visceral and subcutaneous adipose tissue. Biglycan mRNA was noticeably higher in non-adipocytes than adipocytes and significantly decreased during adipogenesis. Adipose tissue biglycan mRNA positively correlated with adiposity indices and insulin resistance parameters; however, this relationship disappeared after adjusting for BMI. In both fat depots, biglycan mRNA strongly correlated with the expression of genes related to inflammation and endoplasmic reticulum stress. In addition, culture of human preadipocytes and differentiated adipocytes under conditions mimicking the local microenvironments of obese adipose tissues significantly increased biglycan mRNA expression. Our data indicate that biglycan gene expression is increased in obese adipose tissues by altered local conditions.

Highlights

IntroductionIs normally sequestered under physiological conditions. in response to tissue stress or damage, the soluble form of biglycan is produced either via partial extracellular matrix (ECM) proteolysis or via de novo synthesis by activated macrophages and other resident cells[10,11]
We investigated the association of biglycan mRNA expression in adipose tissues with other metabolic parameters and the abdominal fat distribution
Remodeling is necessary for adipose tissue expansion in obesity, increased extracellular matrix (ECM) deposition may cause adipose tissue dysfunction[25]

Summary

Introduction

Is normally sequestered under physiological conditions. in response to tissue stress or damage, the soluble form of biglycan is produced either via partial ECM proteolysis or via de novo synthesis by activated macrophages and other resident cells[10,11]. In Psammomys obesus, biglycan expression was strikingly higher in adipose tissues than in all other tissues examined[16]. It was markedly upregulated in the adipose tissues of obese and diabetic individuals compared with lean, normal glucose-tolerant individuals[16]. We compared biglycan expression levels in two separate fat depots, abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT), in obese women (with or without type 2 diabetes) and normal-weight women. To understand how biglycan expression is induced upon obesity, we incubated human preadipocytes as well as differentiated adipocytes in a series of culture environments that could mimic the conditions during obesity

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Conclusion