Abstract
Objective:
To characterize the expression of the small leucine-rich glycoprotein decorin in adipose tissue.
Design:
Real-time PCR was used to measure decorin gene expression in adipose tissue from normal glucose tolerant (NGT), impaired glucose tolerant and type 2 diabetic (T2D) Psammomys obesus. Adipose tissue was fractionated to determine which cells were responsible for decorin expression. The location of decorin protein expression in adipose tissue was determined using immunohistochemistry. Real-time PCR was used to measure decorin mRNA levels in human adipose tissue from 16 insulin-sensitive, 16 insulin-resistant and 6 T2D human subjects. Circulating plasma decorin concentrations were measured by enzyme-linked immunosorbent assay in 145 NGT and 141 T2D human individuals from a large-scale epidemiological study in Mauritius.
Results:
Decorin mRNA was found to be highly expressed in adipose tissue, and decorin gene expression was significantly higher in visceral than that in subcutaneous adipose tissue depots in both P. obesus and human subjects (P=0.002 and P=0.001, respectively). Decorin mRNA was predominantly expressed by stromal/vascular cells of adipose tissue, and decorin protein in adipose tissue was primarily detected adjacent to blood vessels. Circulating plasma decorin levels in humans were elevated by 12% in T2D (P=0.049) compared to NGT subjects. There was a significant independent correlation between plasma decorin levels and waist-to-hip ratio (WHR, P=0.024). In male subjects, plasma decorin levels were significantly correlated with WHR (P=0.006), and fasting and 2-h glucose levels in an oral glucose tolerance test (P=0.027 and P=0.001, respectively).
Conclusions:
Decorin expression in adipose tissue was markedly upregulated in the obese state and may therefore play a role in adipose tissue homeostasis or in pathophysiology associated with obesity.
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Acknowledgements
We gratefully acknowledge Adrian Cooper and Jason Palmer for their valuable technical assistance. This work was financially supported by ChemGenex Pharmaceuticals (Geelong, VIC, Australia). Kristy Bolton is a recipient of a Deakin University postgraduate scholarship. This study was performed in collaboration with the Ministry of Health (Mauritius) and the International Diabetes Institute (Caulfield, Australia). The Mauritius field study was jointly funded by the US National Institutes of Health Grant DK-25446 and the International Diabetes Institute.
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PZ is chairman of the scientific advisor board of ChemGenex Pharmaceuticals. KW and GC are employees of ChemGenex Pharmaceuticals.
Supplementary Information accompanies the paper on International Journal of Obesity website (http://www.nature.com/ijo)
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Bolton, K., Segal, D., McMillan, J. et al. Decorin is a secreted protein associated with obesity and type 2 diabetes. Int J Obes 32, 1113–1121 (2008). https://doi.org/10.1038/ijo.2008.41
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DOI: https://doi.org/10.1038/ijo.2008.41
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