Circulating sDPP-4 is increased in obesity and insulin resistance but is not related to systemic metabolic inflammation.
J Clin Endocrinol Metab. 2020 Oct 21;:
Authors: Rohmann N, Schlicht K, Corinna G, Hollstein T, Knappe C, Krause L, Hagen S, Beckmann A, Seoudy AK, Wietzke-Braun P, Hartmann K, Schulte D, Türk K, Beckmann J, von Schönfels W, Hägele FA, Bosy-Westphal A, Franke A, Schreiber S, Laudes M
Abstract
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.
PMID: 33084870 [PubMed - as supplied by publisher]
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