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人参皂苷Rg1通过激活3T3-L1细胞中的C/EBP同源蛋白10抑制脂肪细胞发育的早期阶段,并减轻高脂饮食诱导的肥胖斑马鱼的脂肪积累。

Ginsenoside Rg1 suppresses early stage of adipocyte development via activation of C/EBP homologous protein-10 in 3T3-L1 and attenuates fat accumulation in high fat diet-induced obese zebrafish.

作者信息

Koh Eun-Jeong, Kim Kui-Jin, Choi Jia, Jeon Hui Jeon, Seo Min-Jung, Lee Boo-Yong

机构信息

Department of Food Science and Biotechnology, College of Life Science, CHA University, Seongnam, Korea.

出版信息

J Ginseng Res. 2017 Jan;41(1):23-30. doi: 10.1016/j.jgr.2015.12.005. Epub 2015 Dec 17.

Abstract

BACKGROUND

Ginsenoside Rg1 is a class of steroid glycoside and triterpene saponin in . Many studies suggest that Rg1 suppresses adipocyte differentiation in 3T3-L1. However, the detail molecular mechanism of Rg1 on adipogenesis in 3T3-L1 is still not fully understood.

METHODS

3T3-L1 preadipocyte was used to evaluate the effect of Rg1 on adipocyte development in the differentiation in a stage-dependent manner . Oil Red O staining and Nile red staining were conducted to measure intracellular lipid accumulation and superoxide production, respectively. We analyzed the protein expression using Western blot . The zebrafish model was used to investigate whether Rg1 suppresses the early stage of fat accumulation .

RESULTS

Rg1 decreased lipid accumulation in early-stage differentiation of 3T3-L1 compared with intermediate and later stages of adipocyte differentiation. Rg1 dramatically increased CAAT/enhancer binding protein (C/EBP) homologous protein-10 (CHOP10) and subsequently reduced the C/EBPβ transcriptional activity that prohibited the initiation of adipogenic marker expression as well as triglyceride synthase. Rg1 decreased the expression of extracellular signal-regulated kinase 1/2 and glycogen synthase kinase 3β, which are also essential for stimulating the expression of CEBPβ. Rg1 also reduced reactive oxygen species production because of the downregulated protein level of nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase 4 (NOX4). While Rg1 increased the endogenous antioxidant enzymes, it also dramatically decreased the accumulation of lipid and triglyceride in high fat diet-induced obese zebrafish.

CONCLUSION

We demonstrated that Rg1 suppresses early-stage differentiation via the activation of CHOP10 and attenuates fat accumulation . These results indicate that Rg1 might have the potential to reduce body fat accumulation in the early stage of obesity.

摘要

背景

人参皂苷Rg1是人参中的一类甾体糖苷和三萜皂苷。许多研究表明,Rg1可抑制3T3-L1细胞的脂肪细胞分化。然而,Rg1对3T3-L1细胞脂肪生成的具体分子机制仍未完全明确。

方法

采用3T3-L1前脂肪细胞,以阶段依赖性方式评估Rg1对脂肪细胞分化发育的影响。分别进行油红O染色和尼罗红染色以测量细胞内脂质积累和超氧化物产生。我们使用蛋白质印迹法分析蛋白质表达。利用斑马鱼模型研究Rg1是否抑制脂肪积累的早期阶段。

结果

与脂肪细胞分化的中期和后期相比,Rg1在3T3-L1细胞早期分化阶段减少了脂质积累。Rg1显著增加了CCAAT/增强子结合蛋白(C/EBP)同源蛋白-10(CHOP10),随后降低了C/EBPβ转录活性,从而阻止脂肪生成标志物表达以及甘油三酯合酶的启动。Rg1降低了细胞外信号调节激酶1/2和糖原合酶激酶3β的表达,这两者对刺激CEBPβ的表达也至关重要。由于烟酰胺腺嘌呤二核苷酸磷酸氢(NADPH)氧化酶4(NOX4)蛋白水平下调,Rg1还减少了活性氧的产生。虽然Rg1增加了内源性抗氧化酶,但它也显著减少了高脂饮食诱导的肥胖斑马鱼中脂质和甘油三酯的积累。

结论

我们证明Rg1通过激活CHOP10抑制早期分化并减轻脂肪积累。这些结果表明,Rg1可能具有在肥胖早期阶段减少体脂积累的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4427/5223064/32f0c9d4c02f/gr1.jpg

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