Modification of adipogenesis and oxidative stress by quercetin: positive or negative impact on adipose tissue metabolism of obese diabetic Zucker rats?

IF 3.7 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Katarína Kršková, Viktória Dobrócsyová, Kristína Ferenczyová, Jana Hricovíniová, Barbora Kaločayová, Ulrika Duľová, Mahdi Bozorgnia, Monika Barteková, Štefan Zorad
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Abstract

Reactive oxygen species (ROS) play a key role in the regulation of adipogenesis. The aim of our study was to investigate the effect of quercetin (QCT) supplement on obese adipose tissue metabolism of 30-week-old diabetic Zucker rats (ZDF), not well examined yet. QCT was administered orally at dose of 20 mg/kg body weight/day for 6 weeks. Adipocytes from subcutaneous adipose tissue (ScWAT) were isolated and their size was evaluated by light microscopy. Gene expression of adipogenic markers in subcutaneous and visceral adipose tissue was determined by real-time PCR and expression of proteins involved in lipid and glucose metabolism was determined in ScWAT by immunoblotting. Obese ZDF rats suffered from diabetes, hyperinsulinemia and had higher index HOMA-IR (Homeostatic Model Assessment for Insulin Resistance). Treatment with QCT had no significant impact on these metabolic disorders in genetic model of obesity and type 2 diabetes used in our study. Nevertheless, QCT reduced expression of inflammatory cytokine tumour necrosis factor alpha in ScWAT and also visceral adipose tissue and up-regulated expression of anti-inflammatory adiponectin in ScWAT. A shift in redox equilibrium was detected via inhibition of pro-oxidant genes by QCT. Furthermore, QCT reduced adipocyte size in ScWAT, down-regulated expression of fatty acid synthase and adipogenic markers, and moreover stimulated expression of proteolytic enzymes. These changes likely resulted in reduced fat deposition in ScWAT, which was reflected in the elevated circulated levels of free fatty acids in QCT-treated obese ZDF rats compared with obese untreated controls. This increase could, at least in part, explain why we did not observe an improvement in systemic metabolic health by QCT in our model. In conclusion, our study suggests that preventive treatment with QCT might be more effective than its administration in the stage of fully developed diabetes, and further research in this area is needed.

槲皮素对脂肪生成和氧化应激的改变:对肥胖糖尿病扎克大鼠脂肪组织代谢的积极影响还是消极影响?
活性氧(ROS)在调控脂肪生成过程中起着关键作用。我们的研究旨在探讨槲皮素(QCT)补充剂对 30 周龄糖尿病扎克大鼠(ZDF)肥胖脂肪组织代谢的影响。按 20 毫克/千克体重/天的剂量口服 QCT,连续服用 6 周。从皮下脂肪组织(ScWAT)中分离出脂肪细胞,并用光学显微镜评估其大小。通过实时 PCR 测定皮下和内脏脂肪组织中脂肪生成标记物的基因表达,并通过免疫印迹法测定 ScWAT 中参与脂质和葡萄糖代谢的蛋白质的表达。肥胖 ZDF 大鼠患有糖尿病和高胰岛素血症,其 HOMA-IR 指数(胰岛素抵抗静态模型评估)较高。在我们研究中使用的肥胖和2型糖尿病遗传模型中,使用QCT治疗对这些代谢紊乱没有明显影响。不过,QCT 降低了炎症细胞因子肿瘤坏死因子α在 ScWAT 和内脏脂肪组织中的表达,并上调了抗炎性脂肪连素在 ScWAT 中的表达。通过 QCT 对促氧化基因的抑制,可以检测到氧化还原平衡的变化。此外,QCT 还缩小了 ScWAT 中的脂肪细胞体积,下调了脂肪酸合成酶和脂肪生成标志物的表达,并刺激了蛋白水解酶的表达。这些变化可能导致 ScWAT 中的脂肪沉积减少,这反映在经 QCT 处理的肥胖 ZDF 大鼠与未经处理的肥胖对照组相比,循环中的游离脂肪酸水平升高。这种升高至少可以部分解释为什么在我们的模型中没有观察到 QCT 对全身代谢健康的改善。总之,我们的研究表明,使用 QCT 进行预防性治疗可能比在糖尿病完全发展阶段使用更有效,因此需要在这一领域开展进一步的研究。
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来源期刊
Journal of physiology and biochemistry
Journal of physiology and biochemistry 生物-生化与分子生物学
CiteScore
6.60
自引率
0.00%
发文量
86
审稿时长
6-12 weeks
期刊介绍: The Journal of Physiology and Biochemistry publishes original research articles and reviews describing relevant new observations on molecular, biochemical and cellular mechanisms involved in human physiology. All areas of the physiology are covered. Special emphasis is placed on the integration of those levels in the whole-organism. The Journal of Physiology and Biochemistry also welcomes articles on molecular nutrition and metabolism studies, and works related to the genomic or proteomic bases of the physiological functions. Descriptive manuscripts about physiological/biochemical processes or clinical manuscripts will not be considered. The journal will not accept manuscripts testing effects of animal or plant extracts.
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