Oxidized LDL upregulates macrophage DPP4 expression via TLR4/TRIF/CD36 pathways

Abstract Background We and others have shown that dipeptidyl peptidase-IV (DPP4) expression is increased in obesity/atherosclerosis and is positively correlated with atherosclerotic burden. However, the mechanism by which DPP4 expression is regulated in obesity remains unclear. In this study, we investigated the pathways regulating the expression of DPP4 on macrophages. Methods Flowsight® Imaging Flow Cytometry was employed for the detection of DPP4 and immunophenotyping. DPP4 enzymatic activity was measured by a DPPIV-Glo™ Protease Assay kit. Findings Human monocytes expressed a moderate level of membrane-bound DPP4. Obese patients with body mass index (BMI) ≥ 30 had a higher level of monocyte DPP4 expression, in parallel with higher levels of HOMA-IR, blood glucose, triglycerides, and non-HDL cholesterol, compared to those in the non-obese (BMI  + cells. OxLDL mediated DPP4 up-regulation was considerably diminished by Toll-like receptor-4 ( TLR4) knockdown and CD36deficiency. TRIFdeficiency, but not MyD88 deficiency, attenuated oxLDL-induced DPP4 increase. Interpretation Our study suggests a key role for oxLDL and downstream CD36/ TLR4/ TRIFin regulating DPP4 expression. Increased DPP4 in response to oxidized lipids may represent an integrated mechanism linking post-prandialglucose metabolism to lipoprotein abnormality-potentiated atherosclerosis.