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. 2022 Mar;61(2):1003-1014.
doi: 10.1007/s00394-021-02714-w. Epub 2021 Oct 26.

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

Mirko Marino  1 , Cristian Del Bo  2 , Massimiliano Tucci  1 , Samuele Venturi  1 , Giacomo Mantegazza  1 , Valentina Taverniti  1 , Peter Møller  3 , Patrizia Riso  1 , Marisa Porrini  1
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Free article

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

Mirko Marino et al. Eur J Nutr. 2022 Mar.
Free article

Abstract

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.

Keywords: Atherosclerosis; C/EBPβ; Lipid accumulation; PPAR-γ1; Phenolic acids; THP-1-derived macrophages.

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