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Coffee Bioactive N-Methylpyridinium Attenuates Tumor Necrosis Factor (TNF)-α-Mediated Insulin Resistance and Inflammation in Human Adipocytes

Department of Biological and Environmental Sciences and Technologies (DISTEBA), University of Salento, 73100 Lecce, Italy
Institute of Clinical Physiology (IFC), National Research Council (CNR), 73100 Lecce, Italy
Cardiovascular Center, Paracelsus Medical University, 90471 Nuremberg, Germany
GVM Care & Research, Città di Lecce Hospital, 73100 Lecce, Italy
Cardiac Surgery Unit, Department of Experimental and Clinical Medicine, University “Magna Graecia”, 88100 Catanzaro, Italy
Division of Pediatric Endocrinology, Diabetes and Obesity, Department of Pediatrics and Adolescent Medicine, University of Ulm, 89075 Ulm, Germany
Human Nutrition Unit, Department of Food and Drugs, University of Parma, 43125 Parma, Italy
Cardiology Division, Pisa University Hospital, 56126 Pisa, Italy
Fondazione Villa Serena per la Ricerca, Città Sant’Angelo, 65013 Pescara, Italy
Authors to whom correspondence should be addressed.
Academic Editor: Joanna Kolniak-Ostek
Biomolecules 2021, 11(10), 1545;
Received: 23 September 2021 / Revised: 12 October 2021 / Accepted: 15 October 2021 / Published: 19 October 2021
Although coffee consumption has been historically associated with negative health outcomes, recent evidence suggests a lower risk of metabolic syndrome, obesity and diabetes among regular coffee drinkers. Among the plethora of minor organic compounds assessed as potential mediators of coffee health benefits, trigonelline and its pyrolysis product N-methylpyridinium (NMP) were preliminary shown to promote glucose uptake and exert anti-adipogenic properties. Against this background, we aimed at characterizing the effects of trigonelline and NMP in inflamed and dysfunctional human adipocytes. Human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes were treated with NMP or, for comparison, trigonelline, for 5 h before stimulation with tumor necrosis factor (TNF)-α. NMP at concentrations as low as 1 µmol/L reduced the stimulated expression of several pro-inflammatory mediators, including C-C Motif chemokine ligand (CCL)-2, C-X-C Motif chemokine ligand (CXCL)-10, and intercellular adhesion Molecule (ICAM)-1, but left the induction of prostaglandin G/H synthase (PTGS)2, interleukin (IL)-1β, and colony stimulating factor (CSF)1 unaffected. Furthermore, NMP restored the downregulated expression of adiponectin (ADIPOQ). These effects were functionally associated with downregulation of the adhesion of monocytes to inflamed adipocytes. Under the same conditions, NMP also reversed the TNF-α-mediated suppression of insulin-stimulated Ser473 Akt phosphorylation and attenuated the induction of TNF-α-stimulated lipolysis restoring cell fat content. In an attempt to preliminarily explore the underlying mechanisms of its action, we show that NMP restores the expression of the master regulator of adipocyte differentiation peroxisome proliferator-activated receptor (PPAR)γ and downregulates activation of the pro-inflammatory mitogen-activated protein jun N-terminal kinase (JNK). In conclusion, NMP reduces adipose dysfunction in pro-inflammatory activated adipocytes. These data suggest that bioactive NMP in coffee may improve the inflammatory and dysmetabolic milieu associated with obesity. View Full-Text
Keywords: coffee bioactives; N-methylpyridinium; adipocytes; inflammation; insulin resistance coffee bioactives; N-methylpyridinium; adipocytes; inflammation; insulin resistance
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MDPI and ACS Style

Quarta, S.; Scoditti, E.; Carluccio, M.A.; Calabriso, N.; Santarpino, G.; Damiano, F.; Siculella, L.; Wabitsch, M.; Verri, T.; Favari, C.; Del Rio, D.; Mena, P.; De Caterina, R.; Massaro, M. Coffee Bioactive N-Methylpyridinium Attenuates Tumor Necrosis Factor (TNF)-α-Mediated Insulin Resistance and Inflammation in Human Adipocytes. Biomolecules 2021, 11, 1545.

AMA Style

Quarta S, Scoditti E, Carluccio MA, Calabriso N, Santarpino G, Damiano F, Siculella L, Wabitsch M, Verri T, Favari C, Del Rio D, Mena P, De Caterina R, Massaro M. Coffee Bioactive N-Methylpyridinium Attenuates Tumor Necrosis Factor (TNF)-α-Mediated Insulin Resistance and Inflammation in Human Adipocytes. Biomolecules. 2021; 11(10):1545.

Chicago/Turabian Style

Quarta, Stefano, Egeria Scoditti, Maria A. Carluccio, Nadia Calabriso, Giuseppe Santarpino, Fabrizio Damiano, Luisa Siculella, Martin Wabitsch, Tiziano Verri, Claudia Favari, Daniele Del Rio, Pedro Mena, Raffaele De Caterina, and Marika Massaro. 2021. "Coffee Bioactive N-Methylpyridinium Attenuates Tumor Necrosis Factor (TNF)-α-Mediated Insulin Resistance and Inflammation in Human Adipocytes" Biomolecules 11, no. 10: 1545.

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