NRF2 Activation Suppressed Methylglyoxal-Lysine Dimer-Induced Oxidative Stress and Inflammatory Paracrine Interaction between Macrophages and Adipocytes

Macrophage infiltration is closely associated with adipocyte-related inflammatory response in obesity. In this study, we explored methylglyoxal-lysine dimer (MOLD)-induced inflammatory responses and metabolic disorders during macrophage and adipocyte interactions using an <i>in vitro</i> conditioned co-culture medium-based. MOLD significantly increased the levels of advanced glycation end products (AGEs) and receptor for AGEs and induced the levels of nitric oxide and prostaglandin E2 in RAW 264.7 cells. Moreover, MOLD-induced inflammatory cytokines, including tumor necrosis factor alpha and interleukin-6, in RAW 264.7 cells. Macrophage-derived conditioned medium induced adipogenesis transcription factors and lipid accumulation in 3T3-L1 cells. NF-E2 p45-related factor 2 (NRF2) activation suppressed the MOLD-induced expression of inflammation- and adipogenesis-related genes in RAW 264.7 cells. These findings suggest that MOLD stimulates inflammatory response and adipogenesis, and NRF2 may be a key modulator of MOLD-induced inflammation and adipogenesis.