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超顺磁性氧化铁纳米颗粒通过调节肝脏脂肪分解和线粒体生物合成介导的抗肥胖作用。

Anti-obesity effects of superparamagnetic iron oxide nanoparticles mediated through modulation of hepatic lipolysis and mitochondrial biogenesis.

作者信息

Salih Reem H A, Oriquat Ghaleb A, AlAdwan Safwan, Ghazal Nesma A, Alsenousy Aisha H A, Assem Nagwa M, Ghareeb Ahmed Z, Kamel Maher A, El-Tahan Rasha A

机构信息

Clinical Chemistry Department, Faculty of Medical Laboratory Sciences, West Kordufan University, Sudan.

Department of Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Al-Ahliyya Amman University, 19328 Amman, Jordan.

出版信息

Gene. 2025 Sep 5;963:149608. doi: 10.1016/j.gene.2025.149608. Epub 2025 Jun 3.

DOI:10.1016/j.gene.2025.149608
PMID:40473063
Abstract

BACKGROUND

Obesity linked to a variety of chronic diseases poses a significant hazard to global health, with consequences for patients in a variety of organ systems. Because superparamagnetic iron oxide nanoparticles (SPIONs) are strong factors having glucose and lipid-lowering effects, this study aimed to examine the possible anti-obesity and anti-steatotic effects of SPIONs by targeting genes involved in lipid and mitochondrial biogenesis regulation in hepatic tissues of an experimental model of obesity.

METHODS

The study was carried out on 72 young male albino rats, divided into 2 groups: the healthy group and the obese group. The obese group was further divided into 8 groups: (a) untreated obese group; (b) orlistat treated group; (c) SPION-550-Dose 22 treated group; (d) SPION-550-Dose 44 treated group; (e) SPION-550-Dose 22-orlistat treated group; (f) SPION-2000-Dose 22 treated group; (g) SPION-2000-Dose 44 treated group; (h) SPION-2000-Dose 22-orlistat treated group.

RESULTS

SPIONs have anti-obesity effects through multiple correlated mechanisms, including reduction of FBS, HOMA-IR, lipid profile, MDA content, and ameliorating activities of both liver enzymes. Also, there was an increase in GSH content, a downregulation of SREBP-1c, and upregulation of PGC-1α, NRF1, and NRF2 expressions. Furthermore, a significant rise in mtDNA copy number in hepatictissues was observed.

CONCLUSIONS

The anti-obesity effects of SPIONs may be mediated by inducing many pathways such as insulin-sensitizing, lipotropic, antioxidant, anti-lipogenic, and mitochondrial biogenesis. More importantly, the adjuvant treatment with orlistat may potentiate the effects of SPION and neglect the use of high SPION doses.

摘要

背景

与多种慢性疾病相关的肥胖对全球健康构成重大危害,会影响多个器官系统的患者。由于超顺磁性氧化铁纳米颗粒(SPIONs)是具有降血糖和降血脂作用的重要因素,本研究旨在通过靶向肥胖实验模型肝组织中参与脂质和线粒体生物合成调节的基因,研究SPIONs可能的抗肥胖和抗脂肪变性作用。

方法

对72只年轻雄性白化大鼠进行研究,分为2组:健康组和肥胖组。肥胖组进一步分为8组:(a)未治疗的肥胖组;(b)奥利司他治疗组;(c)SPION - 550 -剂量22治疗组;(d)SPION - 550 -剂量44治疗组;(e)SPION - 550 -剂量22 -奥利司他治疗组;(f)SPION - 2000 -剂量22治疗组;(g)SPION - 2000 -剂量44治疗组;(h)SPION - 2000 -剂量22 -奥利司他治疗组。

结果

SPIONs通过多种相关机制发挥抗肥胖作用,包括降低空腹血糖(FBS)、稳态模型评估胰岛素抵抗(HOMA - IR)、血脂水平、丙二醛(MDA)含量,改善两种肝酶的活性。此外,谷胱甘肽(GSH)含量增加,固醇调节元件结合蛋白1c(SREBP - 1c)下调,过氧化物酶体增殖物激活受体γ共激活因子1α(PGC - 1α)、核呼吸因子1(NRF1)和核因子E2相关因子2(NRF2)表达上调。此外,观察到肝组织中线粒体DNA(mtDNA)拷贝数显著增加。

结论

SPIONs的抗肥胖作用可能通过诱导多种途径介导,如胰岛素增敏、促脂、抗氧化、抗脂肪生成和线粒体生物合成。更重要的是,与奥利司他联合治疗可能增强SPIONs的作用,并避免使用高剂量的SPIONs。

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