Nε-(carboxymethyl)lysine promotes lipid uptake of macrophage via cluster of differentiation 36 and receptor for advanced glycation end products

Core Tip

Core Tip: N^ε-(carboxymethyl)lysine (CML), a toxic metabolism product in diabetes mellites, is a causative factor of many diseases. CML has been reported to promote lipid uptake in macrophages and foam cell formation. The receptor for advanced glycation end products (RAGE) and cluster of differentiation 36 (CD36) are receptors of CML. However, the roles of RAGE and CD36 in CML-induced lipid uptake in macrophages are currently unclear. Moreover, the relationship and difference between RAGE and CD36 in this process are also worth exploring. The in vitro model was constructed with Raw264.7 cells. Under the stimulation of CML, the lipid uptake by cells was significantly increased. Inhibition of CD36 or RAGE antagonized CML-induced lipid uptake. We synthesized a probe of ¹⁸F-CML to explore the relationship of CML to CD36 and to RAGE. CML could bind to CD36 and to RAGE, and CML has a significantly stronger affinity for CD36 than for RAGE. The exploration of the pathogenic mechanism of CML may provide evidence for a deeper understanding of diseases related to metabolic disorders.