Folate deficiency and leptin resistance are the risk factors for chronic inflammation. The synergistic effect and interaction between these factors remains unclear. In the present study, we aimed to investigate the effect of folate status and leptin on the pro-inflammatory activity of macrophage in vitro. Macrophages cell line RAW264.7 were firstly cultured without (f0) or with (f1) folate medium followed by either (1) lipopolysaccharide (LPS), (2) leptin stimulation or (3) LPS/leptin co-stimulation for 48 hours, respectively. The cytokines production of monocyte chemoattractant protein (MCP)-1, tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6 were subsequently determined by ELISA assay. Compared with folate sufficient (f1), the inflammatory mediators were significantly increased under deficient (f0) status. We also found that folic acid repletion suppressed LPS or LPS/leptin-induced productions of MCP-1 and TNF-α. Further study by replacing fetal bovine serum (FBS) with mice serum from normal-fat-diet fed mice (NF/f0, NF/f1) or high-fat-diet fed mice with or without folate deficiency (HF/f0, HF/f1) were performed. The results also showed that f0 mice serum enhanced MCP-1 and TNF-α productions of LPS-stimulated RAW264.7 cells. However, lower MCP-1, but not TNF-α, secretion was found in cells cultured with HF/f0 serum, suggesting that MCP-1 secretion might be more sensitive to microenvironment. In conclusion, folate deficiency or leptin may exacerbate the inflammatory activity of macrophage.
Key words: folate deficiency; leptin, pro-inflammatory cytokines