A mix of chlorogenic and caffeic acid reduces C/EBPß and PPAR-γ1 levels and counteracts lipid accumulation in macrophages

Purpose Chlorogenic acid (CGA) and caffeic acid (CA) are bioactive compounds in whole grains, berries, apples, some citrus fruits and coffee, which are hypothesized to promote health-beneficial effects on the cardiovascular system. This study aimed to evaluate the capacity of CGA and CA to reduce lipid accumulation in macrophages, recognized as a critical stage in the progression of atherosclerosis. Furtherly, the modulation of CCAAT/enhancer-binding protein β (C/EBPβ) and peroxisome proliferator-activated receptor- γ1 (PPAR-γ1), as transcription factors involved in lipid metabolism, was evaluated. Methods THP-1-derived macrophages were treated for 24 h with 0.03, 0.3, 3 and 30 μM of CGA and CA, tested alone or in combination, and a solution of oleic/palmitic acid (500 μM, 2:1 ratio). Lipid storage was assessed spectrophotometrically through fluorescent staining of cells with Nile red. C/EBPβ and PPAR-γ1 mRNA and protein levels were evaluated by RT-PCR and enzyme-linked immunosorbent assay, respectively. Results The mix of CGA + CA (1:1 ratio) reduced lipid accumulation at all concentrations tested, except for the highest one. The greatest effect ( − 65%; p < 0.01) was observed at the concentration of 0.3 μM for each compound. The same concentration significantly ( p < 0.01) downregulated C/EBPβ and PPAR-γ1 gene expression and reduced their protein levels at 2 h and 24 h, respectively. Conclusion The results indicate that the capacity of CGA + CA mix to reduce lipid storage in macrophages is mediated by a reduction in the expression of transcription factors C/EBPβ and PPAR-γ1.