久坐的生活方式和缺乏运动导致代谢综合征相关的合并症,包括腹部肥胖,2型糖尿病,高脂血症相关心血管疾病(CVD),代谢功能障碍相关脂肪性肝病(MAFLD)。在这项研究中,我们通过维生素D受体评估槲皮素的新型肝/心脏/脂肪保护作用,并阐明了其减少脂毒性的潜在机制,高热量饮食引起代谢综合征的炎症和纤维化。雄性瑞士白化病小鼠用西方饮食和糖水喂养多个时间间隔。抗脂毒性,抗炎,通过油红O评估槲皮素的抗纤维化作用,不同时间点的H&E和TMS染色。血脂谱,炎症标志物(TNF-α,IL-1β,IL-6和MCP-1),纤维化标志物(α-SMA,COL1A1,COL1A2),脂联素,从脂肪的RNA库测量AdipoR2和VDR表达水平,肝脏和心脏组织。此外,使用小鼠3T3-L1脂肪细胞评估槲皮素的降脂和抗脂肪性肝炎作用,大鼠H9c2心肌细胞,和人HepG2肝细胞。我们的研究结果表明,西方饮食喂养槲皮素改善小鼠的血脂和脂毒性。组织病理学检查和基因表达数据显示,槲皮素可减少肝脏和心脏炎症以及纤维化相关标志物。有趣的是,槲皮素治疗可增加血清脂联素水平以及AdipoR2和VDR的mRNA表达。体外实验表明,槲皮素处理后,3T3-L1和脂肪酸处理的肝细胞和心肌细胞的脂质积累减少。这些发现表明槲皮素在代谢综合征相关肥胖中通过VDR激活和随后的Adipo/AdipoR2信号传导对多个器官表现出保护作用。肝损伤,和心脏功能障碍。
A sedentary lifestyle and physical inactivity leads to metabolic syndrome-associated comorbidities involving abdominal obesity, type 2 diabetes, hyperlipidaemia associated Cardiovascular Diseases (CVDs), and Metabolic dysfunction-associated fatty liver disease (MAFLD). In this study, we evaluated the novel hepato/cardio/adipo-protective role of Quercetin via Vitamin D Receptor, and elucidated its underlying mechanisms in reducing lipotoxicity, inflammation and fibrosis in high calorie diet induced metabolic syndrome. Male Swiss albino mice were fed with western diet and sugar water for multiple time intervals. Anti-lipotoxicity, anti-inflammatory, and anti-fibrotic effect of Quercetin was assessed by Oil Red O, H&E and TMS staining at different time points. The lipid profile, mRNA expression of inflammatory markers (TNF- α, IL-1β, IL-6 and MCP-1), fibrotic markers (α-SMA, COL1A1, COL1A2), adiponectin, AdipoR2, and VDR expression levels were measured from RNA pools of adipose, liver and heart tissues. Also, lipid-lowering and anti-steatohepatitic effects of Quercetin was assessed using mouse 3T3-L1 adipocytes, rat H9c2 cardiac cells, and human HepG2 hepatocytes. Our results indicate that, western diet fed mice with Quercetin ameliorated lipid profile and lipotoxicity. Histopathological examination and gene expression data revealed that Quercetin reduced hepatic and cardiac inflammation and fibrosis-associated markers. Interestingly, Quercetin treatment increased the serum levels of adiponectin and mRNA expressions of AdipoR2 and VDR. In-vitro experiments revealed the reduction in lipid accumulation of 3T3-L1 and fatty-acid-treated hepatic and cardiac cells following Quercetin treatment. These findings indicate that Quercetin exhibits a protective role on multiple organs through VDR activation and subsequent Adipo/AdipoR2 signaling in metabolic syndrome associated obesity, hepatic injury, and cardiac dysfunction.