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.