Open Access Increase in Circulating and Adipose Tissue Expression of Secretory Leukocyte Peptidase Inhibitor (SLPI) with Obesity and Diabetes

Abstract: Objective: We have recently identified secretory leukocyte peptidase inhibitor (SLPI), a component of the in-nate host defence in human omental adipose tissue. The objective of this study was to determine if the SLPI secreted by adipose tissue is regulated by changes in obesity. Materials/Methods: Circulating SLPI was measured in lean/overweight (n = 13), obese (n = 10) and obese diabetic (n = 11) male volunteers. SLPI gene expression was measured in subcutaneous adipose tissue fat biopsies from these volun-teers using real time PCR. The regulation of SLPI was further explored in the human SGBS adipocyte cell line. Results: Circulating SLPI shows a small but significant increase in obese (11%; p ≤ 0.05) and obese diabetic volunteers (16%; p ≤ 0.001) when compared with lean/overweight volunteers. There was a corresponding increase in SLPI mRNA in the adipose tissue of obese (800%; p ≤ 0.01) and obese diabetic volunteers (500%; p ≤ 0.001) compared with lean/overweight volunteers. In differentiated human adipocytes, SLPI mRNA is increased by IL-6 (10ng/ml; 318%; p ≤ 0.05), TNFalpha (1ng/ml; 279%; p ≤ 0.005), LPS (100ng/ml; 318%; p ≤ 0.05), insulin (1mM; 321%; p ≤ 0.05) and glu-cose (5 mM; 246%; p ≤ 0.05) while in the preadipocytes SLPI mRNA is decreased by TNF alpha (10ng/ml; 30%; p ≤ 0.05) and LPS (100ng/ml; 42%; p ≤ 0.05) compared to untreated preadipocytes. Conclusions: Circulating SLPI and SLPI gene expression in subcutaneous adipose tissue increases with obesity where it may play a local role in the regulation of the low grade inflammatory response associated with obesity