Circulating sDPP-4 is increased in obesity and insulin resistance but is not related to systemic metabolic inflammation.

CONTEXT Dipeptidylpeptidase (DPP)-4 is a key regulator of the incretin system. It exists in a membrane bound form and a soluble form (= sDPP-4). Initial human studies suggested sDPP-4 to be an adipokine involved in metabolic inflammation. However, recent mechanistic data in genetically modified mice questioned these findings. OBJECTIVES We examined circulating sDPP-4 in a cohort of n = 451 humans with different metabolic phenotypes and during three different weight loss interventions (n = 101) to further clarify its role in human physiology and metabolic diseases. DESIGN sDPP-4 serum concentrations were measured by ELISA and related to several phenotyping data including gut microbiome analysis. RESULTS sDPP-4 increased with age and body weight and was positively associated with insulin resistance and hypertriglyceridemia but was reduced in manifest type 2 diabetes. In addition, we found reduced serum concentrations of sDPP-4 in subjects with arterial hypertension. In contrast to earlier reports, we did not identify an association with systemic markers of inflammation. Impaired kidney and liver functions significantly altered sDPP-4 concentrations while no relation to biomarkers for heart failure was observed. Having found increased levels of sDPP-4 in obesity, we studied surgical (gastric bypass and sleeve gastrectomy) and non-surgical interventions revealing a significant association of sDPP-4 with the improvement of liver function tests but not with changes in body weight. CONCLUSIONS Our data suggest that sDPP-4 is related to hepatic abnormalities in obesity rather than primarily functioning as an adipokine and that sDPP-4 is implicated both, in glucose and lipid metabolism, but not fundamentally in systemic inflammation.