Caffeic and Chlorogenic Acids Synergistically Activate Browning Program in Human Adipocytes: Implications of AMPK- and PPAR-Mediated Pathways

Abstract

Caffeic acid (CA) and chlorogenic acid (CGA) are phenolic compounds claimed to be responsible for the metabolic effects of coffee and tea consumption. Along with their structural similarities, they share common mechanisms such as activation of the AMP-activated protein kinase (AMPK) signaling. The present study aimed to investigate the anti-obesity potential of CA and CGA as co-treatment in human adipocytes. The molecular interactions of CA and CGA with key adipogenic transcription factors were simulated through an in silico molecular docking approach. The expression levels of white and brown adipocyte markers, as well as genes related to lipid metabolism, were analyzed by real-time quantitative PCR and Western blot analyses. Mechanistically, the CA/CGA combination induced lipolysis, upregulated AMPK and browning gene expression and downregulated peroxisome proliferator-activated receptor γ (PPARγ) at both transcriptional and protein levels. The gene expression profiles of the CA/CGA-co-treated adipocytes strongly resembled brown-like signatures. Major pathways identified included the AMPK- and PPAR-related signaling pathways. Collectively, these findings indicated that CA/CGA co-stimulation exerted a browning-inducing potential superior to that of either compound used alone which merits implementation in obesity management. Further, the obtained data provide additional insights on how CA and CGA modify adipocyte function, differentiation and lipid metabolism.

Metabolic and Anti-Inflammatory Protective Properties of Human Enriched Serum Following Artichoke Leaf Extract Absorption: Results from an Innovative Ex Vivo Clinical Trial

“…Mechanistically, dietary luteolin activates browning and thermogenesis in primary mouse adipocytes through an AMPK/PGC1alpha pathway-mediated mechanism [ 36 ]. In the same trend, the combination of chlorogenic and caffeic acids induces lipolysis, upregulates AMPK and browning gene expression (including UCP1) while downregulating peroxisome proliferator-activated receptor γ (PPARγ) at both transcriptional and protein levels [ 37 ]. In this ex vivo clinical study, we did not find any up-regulation of UCP-1 expression despite the down-regulation of PPARγ and AP2 (FABP4).…”

Deeper Insights on Alchornea cordifolia (Schumach. & Thonn.) Müll.Arg Extracts: Chemical Profiles, Biological Abilities, Network Analysis and Molecular Docking

“…The protein data bank (PDB) structures of the target proteins were downloaded from the Protein Data Bank platform ( ) as follows: 1HCQ for estrogen receptor 1 (ESR1), 1QCF for hemopoietic cell kinase (HCK); 3BGZ for pim-1 oncogene (PIM-1); 5I3B for tyrosinase; 1GQR for acethylcholinesterase (AchE). Details about the docking calculations are fully described in our recent paper [ 28 ].…”

Anti-Adipogenic Effect of Alchemilla monticola is Mediated Via PI3K/AKT Signaling Inhibition in Human Adipocytes

“…The human Simpson-Golabi-Behmel syndrome (SGBS) cells were maintained and differentiated according to the optimal conditions described earlier (Wabitsch et al, 2001;Vasileva et al, 2020b). Following initiation of adipogenic differentiation, the cells were repeatedly exposed to treatment with every culture media renewal on day 0, four and eight respectively.…”

“…Medicinal plants have centuries of exploitation, including for weight control, mainly based on an empirical ethnopharmacological knowledge (Vasileva et al, 2018). The multicomponent composition and the chemical complexity of plant extracts contribute to the synergic effect in obesity treatment (Vasileva et al, 2020b;Atanasov et al, 2021). Among the most important advantage of the natural products is that their effect is exerted through modulation in more than one molecular mechanism.…”

“…Among the most important advantage of the natural products is that their effect is exerted through modulation in more than one molecular mechanism. Several possible mechanisms of action are explored for the natural anti-obesity compounds such as suppression of appetite, inhibition of lipid absorption, alteration in adipocyte function and differentiation, effect on β-cells and insulin sensitivity, beneficial effect on the gut microbiota and resolution of the obesity-related chronic inflammation (Min et al, 2013;Hussain et al, 2020;Li et al, 2020;Vasileva et al, 2020b;. However, elucidation of the precise mechanism of action of the plant extracts and the active compound or group of compounds involved in their biological effect is critical for the translation of traditional knowledge towards modern therapeutic applications.…”