A Mix of Chlorogenic and Caffeic Acid Reduces C/EBPß and PPAR-γ1 Levels and Counteracts Lipid Accumulation in Macrophages

Overview

Journal Eur J Nutr

Specialty Nutritional Sciences

Date 2021 Oct 26

PMID 34698900

Citations 8

Authors

Mirko Marino

Cristian Del Bo

Massimiliano Tucci

Samuele Venturi

Giacomo Mantegazza

Valentina Taverniti

Peter Moller

Patrizia Riso

Marisa Porrini

Affiliations

Soon will be listed here.

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.

Citing Articles

The C/EBPβ-SESN2 Axis Promotes M2b Macrophage Polarization Induced by T.cp-MIF to Suppress Inflammation in Thelazia Callipaeda Infection.

Luo B, Gou Y, Cui H, Yin C, Sun D, Li D Inflammation. 2024; .

PMID: 39215929 DOI: 10.1007/s10753-024-02114-2.

Efferocytosis by macrophages in physiological and pathological conditions: regulatory pathways and molecular mechanisms.

Sheng Y, Hu W, Chen S, Zhu X Front Immunol. 2024; 15:1275203.

PMID: 38779685 PMC: 11109379. DOI: 10.3389/fimmu.2024.1275203.

Natural products in atherosclerosis therapy by targeting PPARs: a review focusing on lipid metabolism and inflammation.

Zhang Y, Zhang X, Shi S, Ma C, Lin Y, Song W Front Cardiovasc Med. 2024; 11:1372055.

PMID: 38699583 PMC: 11064802. DOI: 10.3389/fcvm.2024.1372055.

The Impact of the Drying Process on the Antioxidant and Anti-Inflammatory Potential of Dried Ripe Coffee Cherry Pulp Soluble Powder.

Lopez-Parra M, Gomez-Dominguez I, Iriondo-DeHond M, Villamediana Merino E, Sanchez-Martin V, Mendiola J Foods. 2024; 13(7).

PMID: 38611418 PMC: 11011276. DOI: 10.3390/foods13071114.

Berry Dietary Interventions in Metabolic Syndrome: New Insights.

Venturi S, Marino M, Cioffi I, Martini D, Del Bo C, Perna S Nutrients. 2023; 15(8).

PMID: 37111125 PMC: 10142833. DOI: 10.3390/nu15081906.

References

Martini D, Marino M, Angelino D, Del Bo C, Del Rio D, Riso P . Role of berries in vascular function: a systematic review of human intervention studies. Nutr Rev. 2019; 78(3):189-206. DOI: 10.1093/nutrit/nuz053. View

Widmer R, Freund M, Flammer A, Sexton J, Lennon R, Romani A . Beneficial effects of polyphenol-rich olive oil in patients with early atherosclerosis. Eur J Nutr. 2012; 52(3):1223-31. PMC: 3915409. DOI: 10.1007/s00394-012-0433-2. View

Del Bo C, Deon V, Campolo J, Lanti C, Parolini M, Porrini M . A serving of blueberry (V. corymbosum) acutely improves peripheral arterial dysfunction in young smokers and non-smokers: two randomized, controlled, crossover pilot studies. Food Funct. 2017; 8(11):4108-4117. DOI: 10.1039/c7fo00861a. View

Tajik N, Tajik M, Mack I, Enck P . The potential effects of chlorogenic acid, the main phenolic components in coffee, on health: a comprehensive review of the literature. Eur J Nutr. 2017; 56(7):2215-2244. DOI: 10.1007/s00394-017-1379-1. View

Tsao R . Chemistry and biochemistry of dietary polyphenols. Nutrients. 2012; 2(12):1231-46. PMC: 3257627. DOI: 10.3390/nu2121231. View

Singla R, Dubey A, Garg A, Sharma R, Fiorino M, Ameen S . Natural Polyphenols: Chemical Classification, Definition of Classes, Subcategories, and Structures. J AOAC Int. 2019; 102(5):1397-1400. DOI: 10.5740/jaoacint.19-0133. View

Rothwell J, Perez-Jimenez J, Neveu V, Medina-Remon A, Mhiri N, Garcia-Lobato P . Phenol-Explorer 3.0: a major update of the Phenol-Explorer database to incorporate data on the effects of food processing on polyphenol content. Database (Oxford). 2013; 2013:bat070. PMC: 3792339. DOI: 10.1093/database/bat070. View

Erk T, Hauser J, Williamson G, Renouf M, Steiling H, Dionisi F . Structure- and dose-absorption relationships of coffee polyphenols. Biofactors. 2013; 40(1):103-12. DOI: 10.1002/biof.1101. View

Stalmach A, Steiling H, Williamson G, Crozier A . Bioavailability of chlorogenic acids following acute ingestion of coffee by humans with an ileostomy. Arch Biochem Biophys. 2010; 501(1):98-105. DOI: 10.1016/j.abb.2010.03.005. View

10.

Stalmach A, Mullen W, Barron D, Uchida K, Yokota T, Cavin C . Metabolite profiling of hydroxycinnamate derivatives in plasma and urine after the ingestion of coffee by humans: identification of biomarkers of coffee consumption. Drug Metab Dispos. 2009; 37(8):1749-58. DOI: 10.1124/dmd.109.028019. View

11.

Monteiro M, Farah A, Perrone D, Trugo L, Donangelo C . Chlorogenic acid compounds from coffee are differentially absorbed and metabolized in humans. J Nutr. 2007; 137(10):2196-201. DOI: 10.1093/jn/137.10.2196. View

12.

Farah A, Monteiro M, Donangelo C, Lafay S . Chlorogenic acids from green coffee extract are highly bioavailable in humans. J Nutr. 2008; 138(12):2309-15. DOI: 10.3945/jn.108.095554. View

13.

Krga I, Tamaian R, Mercier S, Boby C, Monfoulet L, Glibetic M . Anthocyanins and their gut metabolites attenuate monocyte adhesion and transendothelial migration through nutrigenomic mechanisms regulating endothelial cell permeability. Free Radic Biol Med. 2018; 124:364-379. DOI: 10.1016/j.freeradbiomed.2018.06.027. View

14.

Del Bo C, Marino M, Riso P, Moller P, Porrini M . Anthocyanins and metabolites resolve TNF-α-mediated production of E-selectin and adhesion of monocytes to endothelial cells. Chem Biol Interact. 2019; 300:49-55. DOI: 10.1016/j.cbi.2019.01.002. View

15.

Del Bo C, Cao Y, Roursgaard M, Riso P, Porrini M, Loft S . Anthocyanins and phenolic acids from a wild blueberry (Vaccinium angustifolium) powder counteract lipid accumulation in THP-1-derived macrophages. Eur J Nutr. 2015; 55(1):171-82. DOI: 10.1007/s00394-015-0835-z. View

16.

Gibson M, Domingues N, Vieira O . Lipid and Non-lipid Factors Affecting Macrophage Dysfunction and Inflammation in Atherosclerosis. Front Physiol. 2018; 9:654. PMC: 6029489. DOI: 10.3389/fphys.2018.00654. View

17.

Tabas I . Macrophage apoptosis in atherosclerosis: consequences on plaque progression and the role of endoplasmic reticulum stress. Antioxid Redox Signal. 2009; 11(9):2333-9. PMC: 2787884. DOI: 10.1089/ars.2009.2469. View

18.

Brophy M, Dong Y, Wu H, Rahman H, Song K, Chen H . Eating the Dead to Keep Atherosclerosis at Bay. Front Cardiovasc Med. 2017; 4:2. PMC: 5277199. DOI: 10.3389/fcvm.2017.00002. View

19.

Remmerie A, Scott C . Macrophages and lipid metabolism. Cell Immunol. 2018; 330:27-42. PMC: 6108423. DOI: 10.1016/j.cellimm.2018.01.020. View

20.

Batista-Gonzalez A, Vidal R, Criollo A, Carreno L . New Insights on the Role of Lipid Metabolism in the Metabolic Reprogramming of Macrophages. Front Immunol. 2020; 10:2993. PMC: 6966486. DOI: 10.3389/fimmu.2019.02993. View