Joshi Christie, Jadeja Viren, Zhou Heping
Department of Biological Sciences, Seton Hall University, South Orange, NJ 07079, USA.
Int J Mol Sci. 2021 Jul 1;22(13):7127. doi: 10.3390/ijms22137127.
The coronavirus disease 2019 (COVID-19) pandemic has claimed over 2.7 million lives globally. Obesity has been associated with increased severity and mortality of COVID-19. However, the molecular mechanisms by which obesity exacerbates COVID-19 pathologies are not well-defined. The levels of free fatty acids (FFAs) are elevated in obese subjects. This study was therefore designed to examine how excess levels of different FFAs may affect the progression of COVID-19. Biological molecules associated with palmitic acid (PA) and COVID-19 were retrieved from QIAGEN Knowledge Base, and Ingenuity Pathway Analysis tools were used to analyze these datasets and explore the potential pathways affected by different FFAs. Our study found that one of the top 10 canonical pathways affected by PA was the coronavirus pathogenesis pathway, mediated by key inflammatory mediators, including PTGS2; cytokines, including IL1β and IL6; chemokines, including CCL2 and CCL5; transcription factors, including NFκB; translation regulators, including EEF1A1; and apoptotic mediators, including BAX. In contrast, n-3 fatty acids may attenuate PA's activation of the coronavirus pathogenesis pathway by inhibiting the activity of such mediators as IL1β, CCL2, PTGS2, and BAX. Furthermore, PA may modulate the expression of ACE2, the main cell surface receptor for the SARS-CoV-2 spike protein.
2019冠状病毒病（COVID-19）大流行已在全球夺走了超过270万人的生命。肥胖与COVID-19病情加重及死亡率增加有关。然而，肥胖加剧COVID-19病理的分子机制尚不清楚。肥胖受试者体内游离脂肪酸（FFA）水平升高。因此，本研究旨在探讨不同FFA的过量水平如何影响COVID-19的进展。从QIAGEN知识库中检索与棕榈酸（PA）和COVID-19相关的生物分子，并使用Ingenuity通路分析工具分析这些数据集，探索受不同FFA影响的潜在通路。我们的研究发现，PA影响的前10条典型通路之一是冠状病毒发病机制通路，由关键炎症介质介导，包括PTGS2；细胞因子，包括IL1β和IL6；趋化因子，包括CCL2和CCL5；转录因子，包括NFκB；翻译调节因子，包括EEF1A1；以及凋亡介质，包括BAX。相比之下，n-3脂肪酸可能通过抑制IL1β、CCL2、PTGS2和BAX等介质的活性来减弱PA对冠状病毒发病机制通路的激活。此外，PA可能调节ACE2的表达，ACE2是SARS-CoV-2刺突蛋白的主要细胞表面受体。
