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 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.

A dietary carbohydrate – gut Parasutterella – human fatty acid biosynthesis metabolic axis in obesity and type 2 diabetes

“…For validation of 16S rRNA gene sequencing data, we performed quantitative polymerase chain reaction (qPCR) for Parasutterella excrementihominis of n = 55 patients of an intervention cohort described elsewhere 21 ( Table 1 ). In brief, this group of severely overweight patients underwent a dietary intervention that consisted of a very low-calorie formula diet for the duration of 12 weeks, followed by a stabilization period of another 14 weeks.…”

Adipose Tissue Secretion Pattern Influences β-Cell Wellness in the Transition from Obesity to Type 2 Diabetes

“…The release of DPP-4 is strongly correlated to the size of adipocytes, with an expression 5 times higher in VAT than SAT in obese subjects [ 139 ]. Serum DPP-4 levels are significantly higher in obese than normal-weight subjects, and are positively associated with fasting blood glucose and insulin concentrations as well as with insulin resistance index (HOMA-IR) [ 140 , 141 , 142 ]. In addition, no significant differences in DPP-4 levels were found between obese patients with T2D and obese non-diabetic subjects [ 142 ], although the difference in the enzymatic activity rather than in circulating levels should be evaluated.…”

The Expression of Genes Related to Lipid Metabolism and Metabolic Disorders in Children before and after Hematopoietic Stem Cell Transplantation—A Prospective Observational Study

“…According to their observations in a group of 92 obese premenopausal women, DPP4 expression correlated (r = 0.25) with plasma HDL-C/TC ratio [ 39 ]. In a cohort of 451 patients (median age 56 years), correlations between DPP4 and fasting glucose (r = 0.218), insulin (r = 0.196), HOMA-IR (r = 0.210), and TG (r = 0.201) levels were shown [ 40 ]. A similar study was conducted in a group of 93 non-obese patients with type 2 diabetes.…”