Objective: To investigate the impact of metformin (Met) on THP-1 macrophage-derived foam cell formation induced by lipopolysaccharide (LPS) and observe the changes of lipid droplets (LDs) and LDs-associated proteins.
Methods: THP-1 cells were induced to differentiate into macrophages by 100 ng/mL phorbol 12-myristate 13-acetate (PMA) for 48 hours, and then the macrophages were further induced to generate foam cells by 50 μg/mL oxidized low-density lipoprotein (ox-LDL) and 1 μg/mL LPS. During this process, these foam cells were treated with 0, 100, 200 μmol/L Met. Under the fluorescence microscope, the effect of Met on foam cell formation was evaluated by Oil red O staining and the number and morphology of LDs were observed by BODIPY493/503 staining. Intracellular triglyceride (TG) were extracted and measured by TG quantitative kits. The expressions of adipose differentiation-related protein (ADRP) and tail-interacting protein of 47 kDa (TIP47) were detected by Western blotting.
Results: Compared with the untreated group, the LDs in foam cells were reduced significantly and the size became smaller after treated with 100 or 200 μmol/L Met. What's more, the quantitative data showed that the intracellular TG content decreased markedly in a dose-dependent manner, and the TG content decreased about 25% in foam cells treated with 200 μmol/L Met. Western blotting showed that Met reduced the expression of ADRP, but not TIP47 in the THP-1 macrophage-derived foam cells.
Conclusion: Met could inhibit THP-1-derived foam cell formation induced by LPS, reduce intracellular lipid accumulation, and down-regulate the expression of ADRP.