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

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.

Validation of optimal reference genes for quantitative real time PCR in muscle and adipose tissue for obesity and diabetes research

“…The validation of RGs for normalization needs to be considered in the experimental design of studies based on qPCR. Despite β-actin being often employed as the sole reference gene for RT-qPCR data normalization 14 , 48 – 50 , our current study showed that β-actin was one of the most unstable genes in almost all the models assessed. Our data are in agreement with a recent study from Li et al .…”

“…Despite the growing need for increased accuracy and reliability of data generated using RT-qPCR, commonly used RGs are still employed without further validation, or have been found to be unstable in different tissues and physiological conditions 14 – 16 . Thus, the current study aimed to identify suitable RGs to perform quantitative transcriptomic analysis based on RT-qPCR for obesity and diabetes research, employing in vitro models, mouse models and human tissue samples.…”

Biglycan gene connects metabolic dysfunction with brain disorder

“…Although biglycan is present in adipose tissue in the obese state, its action is poorly understood [14,34]. Pathway enrichment analysis of the differentially expressed genes in the liver tissue between Bgn 0/− and WT mice indicate alterations in numerous metabolic related pathways, including metabolism of lipid and lipoprotein, metabolism of amino acids and derivatives, and fundamental cell metabolic processes.…”

“…Biglycan has also been related with low grade inflammatory state in obesity and type 2 diabetes and development of insulin resistance [13,14]. More recently, biglycan has been associated with a broad range of neurode-generative events and disorders such as amyloid metabolism in Alzheimer’s disease pathology [15], inhibition of neurite outgrowth in sensory neurons [16], and neocortical neuronal survival [12,17,18].…”

Enhanced ANGPTL2 expression in adipose tissues and its association with insulin resistance in obese women

“…Adipocyte size was estimated using the mean cross-sectional area of adipocytes in hematoxylin and eosin (H&E)-stained sections of adipose tissue, as previously described 31 . Paired samples of VAT and SAT were obtained from a subgroup of subjects.…”