Circulating sDPP-4 is Increased in Obesity and Insulin Resistance but Is Not Related to Systemic Metabolic Inflammation

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 modifi...

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Published in:The journal of clinical endocrinology and metabolism 2021-02, Vol.106 (2), p.e592-e601
Main Authors: Rohmann, Nathalie, Schlicht, Kristina, Geisler, Corinna, Hollstein, Tim, Knappe, Carina, Krause, Laura, Hagen, Stefanie, Beckmann, Alexia, Seoudy, Anna Katharina, Wietzke-Braun, Perdita, Hartmann, Katharina, Schulte, Dominik, Türk, Kathrin, Beckmann, Jan, von Schönfels, Witigo, Hägele, Franziska Anna, Bosy-Westphal, Anja, Franke, Andre, Schreiber, Stefan, Laudes, Matthias
Format: Article
Language:English
Subjects:
Analysis
Body weight
Body weight loss
Congestive heart failure
Diabetes mellitus (non-insulin dependent)
Enzyme-linked immunosorbent assay
Enzymes
Gastrectomy
Gastric bypass
Genetically modified organisms
Glucose metabolism
Hypertriglyceridemia
Inflammation
Insulin resistance
Intestinal microflora
Lipid metabolism
Liver
Metabolic disorders
Metabolism
Mice
Microbiomes
Obesity
Phenotypes
Phenotyping
Physiological aspects
Sitagliptin
Surgery
Type 2 diabetes
Weight control
Weight loss
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Summary: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 has questioned these findings. Objectives We examined circulating sDPP-4 in a cohort of n = 451 humans with different metabolic phenotypes and during 3 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 enzyme-linked immunosorbent assay 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 nonsurgical interventions, revealing a significant association of sDPP-4 with 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 in lipid metabolism, but not fundamentally in systemic inflammation.
ISSN:0021-972X
1945-7197
DOI:10.1210/clinem/dgaa758