Coffee Bioactive N-Methylpyridinium Attenuates Tumor Necrosis Factor (TNF)-α-Mediated Insulin Resistance and Inflammation in Human Adipocytes.
Stefano QuartaEgeria ScodittiMaria Annunziata CarluccioNadia CalabrisoGiuseppe SantarpinoFabrizio DamianoLuisa SiculellaMartin WabitschTiziano VerriClaudia FavariDaniele Del RioPedro MenaRaffaele De CaterinaMarika MassaroPublished in: Biomolecules (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.
Keyphrases
- insulin resistance
- adipose tissue
- high fat diet induced
- metabolic syndrome
- rheumatoid arthritis
- type diabetes
- high fat diet
- poor prognosis
- endothelial cells
- polycystic ovary syndrome
- glycemic control
- skeletal muscle
- cell proliferation
- induced pluripotent stem cells
- pluripotent stem cells
- uric acid
- binding protein
- oxidative stress
- healthcare
- signaling pathway
- body mass index
- mental health
- public health
- bone marrow
- tyrosine kinase
- cell adhesion
- cardiovascular disease
- cell therapy
- big data
- weight loss
- endoplasmic reticulum stress
- cell death
- deep learning
- heavy metals
- risk assessment
- machine learning
- blood pressure
- newly diagnosed
- weight gain
- candida albicans
- pseudomonas aeruginosa
- mesenchymal stem cells