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来自普通小麦的类黄酮通过上调Insig途径抑制3T3-L1细胞的脂肪生成。

Flavonoids from Triticum aestivum inhibit adipogenesis in 3T3-L1 cells by upregulating the insig pathway.

作者信息

Poudel Barun, Nepali Sarmila, Xin Mingjie, Ki Hyeon-Hui, Kim Young-Ho, Kim Dae-Ki, Lee Young-Mi

机构信息

Department of Oriental Pharmacy, College of Pharmacy and Wonkwang‑Oriental Medicines Research Institute, Wonkwang University, Iksan, Jeonbuk 570‑749, Republic of Korea.

Department of Immunology and Institute of Medical Sciences, Medical School, Chonbuk National University, Jeonju, Jeonbuk 561‑756, Republic of Korea.

出版信息

Mol Med Rep. 2015 Aug;12(2):3139-45. doi: 10.3892/mmr.2015.3700. Epub 2015 Apr 29.

DOI:10.3892/mmr.2015.3700
PMID:25936595
Abstract

The present study aimed to compare the potential anti-adipogenic effects and underlying mechanisms of the luteolin, isoscoparin and isoorientin flavonoids, purified from Triticum aestivum sprout (TA) in 3T3-L1 cells. The cells were treated with different concentrations of flavonoids for 8 days and the lipid accumulation was assessed using Oil-Red-O staining. The expression levels of the transcription factors and the genes involved in adipogenesis in the cells were assessed by reverse transcription-quantitative polymerase chain reaction and western blotting. The results demonstrated that 10 μM luteolin, isoscoparin or isoorientin inhibited lipid deposition in the cells by 74, 63 and 65%, respectively. The flavonoids also significantly inhibited the transcriptional regulators of adipogenesis, including peroxisome proliferator-activated receptor-γ, CAAT/enhancer binding protein-α and sterol regulatory element binding protein (SREBP)-1c, compared with the control cells. Similarly, there was a significant downregulation of the adipocyte specific markers associated with lipid metabolism, including activating protein-2, fatty acid synthase, hormone-sensitive lipase and lipoprotein lipase, in the flavonoid treated cells. Notably, the cells treated with the flavonoids demonstrated increased expression levels of the insulin-induced genes, insig-1 and insig-2, which may have inhibited the activation of the adipogenic transcription factor, SREBP, eventually leading to the inhibition of adipogenesis. Taken together, these results revealed that the flavonoids from TA possessed an inhibitory effect on adipogenesis through downregulation of adipogenic transcription factors and genes associated with lipid metabolism, and the upregulation of insig 1 and 2, suggesting that the flavonoids from TA may be potential therapeutic agents for the prevention and treatment of obesity.

摘要

本研究旨在比较从普通小麦芽(TA)中纯化得到的木犀草素、异鼠李素和异荭草素黄酮类化合物在3T3-L1细胞中的潜在抗脂肪生成作用及其潜在机制。用不同浓度的黄酮类化合物处理细胞8天,并使用油红O染色评估脂质积累。通过逆转录定量聚合酶链反应和蛋白质免疫印迹法评估细胞中参与脂肪生成的转录因子和基因的表达水平。结果表明,10 μM木犀草素、异鼠李素或异荭草素分别使细胞中的脂质沉积减少了74%、63%和65%。与对照细胞相比,这些黄酮类化合物还显著抑制了脂肪生成的转录调节因子,包括过氧化物酶体增殖物激活受体-γ、CAAT/增强子结合蛋白-α和固醇调节元件结合蛋白(SREBP)-1c。同样,在经黄酮类化合物处理的细胞中,与脂质代谢相关的脂肪细胞特异性标志物,包括激活蛋白-2、脂肪酸合酶、激素敏感性脂肪酶和脂蛋白脂肪酶,也有显著下调。值得注意的是,用黄酮类化合物处理的细胞中胰岛素诱导基因insig-1和insig-2的表达水平升高,这可能抑制了脂肪生成转录因子SREBP的激活,最终导致脂肪生成受到抑制。综上所述,这些结果表明,TA中的黄酮类化合物通过下调脂肪生成转录因子和与脂质代谢相关的基因以及上调insig 1和2来抑制脂肪生成,这表明TA中的黄酮类化合物可能是预防和治疗肥胖症的潜在治疗药物。

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