Circulating DKK1 levels are significantly elevated in obese individuals and are associated with insulin resistance and oxidative stress

Abstract

Dickkopf-1 (DKK1) is reportedly involved in various biological functions of the human body. However, the relationship between DKK1 and obesity in humans remains unknown. Bioinformatics analysis was performed to investigate the associations between DKK1 and metabolism-related genes and signaling pathways. EHC and OGTT were performed on all individuals. Serum DKK1 concentrations were measured by an ELISA kit. DKK1 expression was measured by qRT-PCR and Western blotting. We found that circulating DKK1 levels in overweight/obese (OW/OB) individuals were significantly elevated and were associated with parameters of glucose/lipid metabolism and IR, including BMI, WHR, fat%, TC, TG, FBG, 2 h-BG, FIns, 2 h-Ins, LDL-C, HbA1c, HOMA-IR, AUCi, AUCg, BAI, and VAI. The circulating DKK1 concentration was not affected by blood glucose or serum insulin levels. Bioinformatics analysis suggested that DKK1 may be associated with glucose/lipid metabolism and oxidative stress. At the cellular level, we found that DKK1 promoted oxidative stress and inhibited insulin signaling. Circulating DKK1 may be a biomarker for obesity and IR.

Keywords: DKK1; cross‐sectional study; insulin resistance; obesity; oxidative stress.