Adipose DPP4 and obesity: correlation with insulin resistance and depot-specific release from adipose tissue in vivo and in vitro

Objective: To study expression of the recently identified adipokine dipeptidyl peptidase 4 (DPP4) in subcutaneous (SAT) and visceral adipose tissue (VAT) of patients with different BMI and insulin sensitivity as well as to assess circulating DPP4 in relation to obesity and insulin sensitivity. Research Design and Methods: DPP4 expression was measured in SAT and VAT from 196 subjects with a wide range of BMI and insulin sensitivity. DPP4 release was measured ex vivo in paired biopsies from SAT and VAT as well as in vivo from SAT of lean and obese patients. Circulating DPP4 was measured in insulin-sensitive and insulin-resistant BMI-matched obese patients. Results: DPP4 expression positively correlated to BMI both in SAT and VAT with VAT constantly displaying higher expression compared to SAT. Ex vivo release of DPP4 from adipose tissue explants was higher from VAT as compared to SAT in lean and obese patients with obese patients displaying higher DPP4 release compared to lean controls. Net release of DPP4 from adipose tissue was also demonstrated in vivo with greater release in obese subjects compared with lean, and women compared with men. Insulin-sensitive obese patients had significantly lower circulating DPP4 as compared to obesity-matched insulin-resistant patients. Here, DPP4 positively correlated with the amount of VAT, adipocyte size and adipose tissue inflammation. Conclusions: DPP4 is a novel adipokine with higher release from VAT that is particularly pronounced in obese and insulin-resistant patients. Our data suggest that DPP4 might be a marker for visceral obesity and the metabolic syndrome.