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硝酸镧通过干扰有丝分裂克隆扩展过程来抑制 3T3-L1 前脂肪细胞的脂肪生成。

Lanthanum nitrate inhibits adipogenesis in 3T3-L1 preadipocytes with a disorder of mitotic clonal expansion process.

机构信息

Department of Toxicology, School of Public Health, Peking University, Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing, 100191, China.

出版信息

J Appl Toxicol. 2023 Mar;43(3):402-415. doi: 10.1002/jat.4391. Epub 2022 Sep 19.

Abstract

Lanthanum (La) as a rare earth element is widely used in agriculture, industry, and medicine. It has been suggested in several studies that La might influence glycolipid metabolism in vivo. In this study, we used 3T3-L1 preadipocytes as in vitro cell model to elucidate the effects of La(NO ) on adipogenesis and the underlying mechanisms. The results showed that La(NO ) could inhibit the adipogenic differentiation of 3T3-L1 preadipocytes, which showed a decrease in lipid accumulation and the downregulation of specific adipogenic transcription factors. La(NO ) exerted its inhibitory effect mainly at the early differentiation stage. Furthermore, La(NO ) influenced the S-phase entry and cell cycle process during the mitotic clonal expansion and regulated the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and expressions of the proteins in phosphatidylinositol 3-kinase (PI3K)/Akt pathway at the early stage of differentiation. Besides, La(NO ) upregulated the expressions of wnt10b mRNA and β-catenin protein and promoted the nucleus translocation of β-catenin. Additionally, we found that La(NO ) could promote the growth of 3T3-L1 preadipocytes both with and without MDI (3-isobutyl-1-methylxanthine [IBMX], dexamethasone [Dex], and insulin) stimulation. Collectively, these results indicated that La(NO ) could inhibit adipogenesis in 3T3-L1 preadipocytes and influence cell proliferation.

摘要

镧(La)作为一种稀土元素,广泛应用于农业、工业和医药领域。多项研究表明,镧可能会影响体内糖脂代谢。本研究采用 3T3-L1 前脂肪细胞作为体外细胞模型,探讨硝酸镧(La(NO )对脂肪生成的影响及其作用机制。结果表明,La(NO )可抑制 3T3-L1 前脂肪细胞的脂肪生成,表现为脂滴积累减少和特异性脂肪生成转录因子表达下调。La(NO )主要在早期分化阶段发挥抑制作用。此外,La(NO )影响有丝分裂克隆扩张过程中的 S 期进入和细胞周期进程,并在分化早期调控信号转导和转录激活因子 3(STAT3)的磷酸化和磷脂酰肌醇 3-激酶(PI3K)/Akt 通路蛋白的表达。此外,La(NO )还上调 wnt10b mRNA 和 β-连环蛋白蛋白的表达,促进β-连环蛋白向核内转位。另外,我们发现 La(NO )可促进有丝分裂原(3-异丁基-1-甲基黄嘌呤[IBMX]、地塞米松[Dex]和胰岛素)刺激或不刺激的 3T3-L1 前脂肪细胞的生长。综上所述,这些结果表明 La(NO )可抑制 3T3-L1 前脂肪细胞的脂肪生成,并影响细胞增殖。

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