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

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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.

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Acknowledgements

We are grateful to Jacopo Tadini for the support in the experiments. The authors are grateful for support granted by Ministero delle Politiche Agricole, Alimentari e Forestali (Mipaaf) and the European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL) MaPLE. This work was supported by a contribution of the “Piano di sostegno alla ricerca- Linea 2, azione A-grant number PSR2018-2019 CDELB”. P.R. and C.D.B. acknowledge the European Cooperation for Science and Technology (COST Action) CA16112 “NutRedOx: Personalized Nutrition in Aging Society: Redox Control of Major Age-related Diseases”. The results provided in the present manuscript were obtained in the DeFENS Cell Culture Laboratory (University of Milan, Italy).”

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Authors and Affiliations

  1. Department of Food, Environmental and Nutritional Sciences (DeFENS), Università Degli Studi Di Milano, 20133, Milan, Italy

    Mirko Marino, Cristian Del Bo′, Massimiliano Tucci, Samuele Venturi, Giacomo Mantegazza, Valentina Taverniti, Patrizia Riso & Marisa Porrini

  2. Department of Public Health, Section of Environmental Health, University of Copenhagen, 1014, Copenhagen K, Denmark

    Peter Møller

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  1. Mirko Marino
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  2. Cristian Del Bo′
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  3. Massimiliano Tucci
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Contributions

M.M. performed the experiments and wrote the first draft of the manuscript, C.D.B. designed the study, performed part of the experiments, the statistical analysis and wrote the first draft of the manuscript. M.T. and G. M. performed the experiments on gene expression supervised by V.T. S.V. performed the experiments on lipid accumulation supervised by M.M. P.R. and M.P. critically revised the manuscript and partially supported the research. P.M. critically revised the manuscript and edited the paper for language. All authors have read and approved the final version of the manuscript.

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Correspondence to Cristian Del Bo′.

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Marino, M., Del Bo′, C., Tucci, M. et al. A mix of chlorogenic and caffeic acid reduces C/EBPß and PPAR-γ1 levels and counteracts lipid accumulation in macrophages. Eur J Nutr 61, 1003–1014 (2022). https://doi.org/10.1007/s00394-021-02714-w

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  • DOI: https://doi.org/10.1007/s00394-021-02714-w

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