Vasileva Liliya V, Savova Martina S, Amirova Kristiana M, Balcheva-Sivenova Zhivka, Ferrante Claudio, Orlando Giustino, Wabitsch Martin, Georgiev Milen I
Department of Plant Cell Biotechnology, Center of Plant Systems Biology and Biotechnology, 4000 Plovdiv, Bulgaria.
Laboratory of Metabolomics, The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 4000 Plovdiv, Bulgaria.
Int J Mol Sci. 2020 Dec 21;21(24):9740. doi: 10.3390/ijms21249740.
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.
咖啡酸（CA）和绿原酸（CGA）是酚类化合物，据称它们与饮用咖啡和茶所产生的代谢效应有关。除了结构相似外，它们还具有共同的机制，如激活AMP激活的蛋白激酶（AMPK）信号通路。本研究旨在探讨CA和CGA联合处理对人脂肪细胞的抗肥胖潜力。通过计算机模拟分子对接方法，模拟了CA和CGA与关键脂肪生成转录因子的分子相互作用。通过实时定量PCR和蛋白质印迹分析，分析了白色和棕色脂肪细胞标志物以及与脂质代谢相关基因的表达水平。从机制上讲，CA/CGA组合在转录和蛋白质水平上均诱导了脂肪分解，上调了AMPK和棕色化基因的表达，并下调了过氧化物酶体增殖物激活受体γ（PPARγ）。CA/CGA联合处理的脂肪细胞的基因表达谱与棕色样特征非常相似。确定的主要途径包括与AMPK和PPAR相关的信号通路。总的来说，这些发现表明，CA/CGA联合刺激产生的棕色化诱导潜力优于单独使用的任何一种化合物，这在肥胖管理中值得应用。此外，所获得的数据为CA和CGA如何改变脂肪细胞功能、分化和脂质代谢提供了更多见解。
