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

Nathalie Rohmann, Kristina Schlicht, Geisler Corinna, Tim Hollstein, Carina Knappe, Laura Krause, Stefanie Hagen, Alexia Beckmann, Anna Katharina Seoudy, Perdita Wietzke-Braun, Katharina Hartmann, Dominik Schulte, Kathrin Türk, Jan Beckmann, Witigo von Schönfels, Franziska Anna Hägele, Anja Bosy-Westphal, Andre Franke, Stefan Schreiber, Matthias Laudes
Year of publication:
Journal title abbreviated:
J. Clin. Endocrinol. Metab.
Journal title long:
The Journal of clinical endocrinology and metabolism
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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.