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

Objective: We have recently identified secretory leukocyte peptidase inhibitor (SLPI), a component of the innate 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 volunteers 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 glucose (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.