Maleki Mohammad Hasan, Abdizadeh Javazm Sara, Dastghaib Sanaz, Panji Anahita, Hojjati Far Mohammad, Mahmoodi Hajar, Siri Morvarid, Shafiee Sayed Mohammad
Department of Clinical Biochemistry School of Medicine Shiraz University of Medical Sciences Shiraz Iran.
Department of Microbiology Faculty of Sciences Karaj Branch Islamic Azad University Karaj Iran.
Obes Sci Pract. 2024 Apr 13;10(2):e752. doi: 10.1002/osp4.752. eCollection 2024 Apr.
Lipotoxicity, caused by adipocyte triglyceride over-accumulation, contributes to obesity-related comorbidities such as hypertension, type 2 diabetes, coronary heart disease, respiratory dysfunction, and osteoarthritis. This study focuses on determining how sirtuin-1 (SIRT-1) mediates quercetin's (QCT) effect on 3T3-L1 adipocytes. Key aspects of this study include preventing adipogenesis, inducing lipolysis, and stimulating adipocyte apoptosis.
3T3-L1 adipocytes underwent treatment with varying QCT doses, lipopolysaccharide (LPS), and the SIRT-1 inhibitor EX-527, followed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide [MTT] assay for cell viability assessment. Furthermore, quantitative real-time polymerase chain reaction measured mRNA expression levels of adipogenesis markers ( [] and []), lipolysis markers ( [] and []), and apoptosis markers ( and ).
The data showed that LPS + QCT significantly reduced cell viability in a dose- and time-dependent manner, unaffected by LPS + QCT + EX-527. Treatment with LPS + QCT did not affect and expression but significantly increased and mRNA expression compared with LPS alone. Interestingly, EX-527 reversed the effects of LPS + QCT on lipogenesis and lipolysis markers completely. QCT enhanced apoptosis in a SIRT-1 independent pattern.
The data suggest that QCT suppresses adipogenesis while increasing lipolysis via SIRT-1. However, QCT's effects on apoptosis appear to be independent of SIRT-1. These findings provide further evidence for QCT's effects on adipocytes, particularly its interaction with SIRT-1.
脂肪细胞甘油三酯过度蓄积导致的脂毒性会引发与肥胖相关的合并症，如高血压、2型糖尿病、冠心病、呼吸功能障碍和骨关节炎。本研究聚焦于确定沉默调节蛋白1（SIRT-1）如何介导槲皮素（QCT）对3T3-L1脂肪细胞的作用。本研究的关键方面包括预防脂肪生成、诱导脂肪分解和刺激脂肪细胞凋亡。
用不同剂量的QCT、脂多糖（LPS）和SIRT-1抑制剂EX-527处理3T3-L1脂肪细胞，然后用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基-2H-四唑溴盐[MTT]法评估细胞活力。此外，定量实时聚合酶链反应检测脂肪生成标志物（[]和[]）、脂肪分解标志物（[]和[]）以及凋亡标志物（和）的mRNA表达水平。
数据显示，LPS + QCT以剂量和时间依赖性方式显著降低细胞活力，而LPS + QCT + EX-527对其无影响。与单独使用LPS相比，LPS + QCT处理不影响[]和[]的表达，但显著增加[]和[]的mRNA表达。有趣的是，EX-527完全逆转了LPS + QCT对脂肪生成和脂肪分解标志物的影响。QCT以不依赖SIRT-1的方式增强细胞凋亡。
数据表明，QCT通过SIRT-1抑制脂肪生成，同时增加脂肪分解。然而，QCT对细胞凋亡的作用似乎独立于SIRT-1。这些发现为QCT对脂肪细胞的作用，特别是其与SIRT-1的相互作用提供了进一步的证据。
