Alpha-glucosidase inhibitor 1-Deoxynojirimycin promotes beige remodeling of 3T3-L1 preadipocytes via activating AMPK.

Alpha-glucosidase inhibitor 1-Deoxynojirimycin promotes beige remodeling of 3T3-L1 preadipocytes via activating AMPK.
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α-葡萄糖苷酶抑制剂 1-Deoxynojirimycin 通过激活 AMPK 促进 3T3-L1 前脂肪细胞的米色重塑。

DOI:
10.1016/j.bbrc.2019.01.023
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发表时间:
2019-01
期刊:
Biochem Biophys Res Commun.
影响因子:
--
通讯作者:
Yang ZC
Yang ZC
中科院分区:
其他
文献类型:
--
作者:
Li AN;Chen JJ;Li QQ;Zeng GY;Chen QY;Chen JL;Liao ZM;Jin P;Wang KS;Yang ZC

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肥胖症是一个严重的健康问题,寻找有效的治疗肥胖症的药物具有重要意义。1-去氧野尻霉素(DNJ)是从桑葚中提取的,是一种α-葡萄糖苷酶抑制剂,可降低血糖。近年来的研究表明,它也具有减肥作用,但其作用机制尚不清楚。在我们目前的研究中,我们主要研究DNJ对3 T3-L1前脂肪细胞米色重塑的影响。DNJ对未分化前脂肪细胞中脂肪酸结合蛋白4(aP 2)、过氧化物酶体增殖物激活受体γ(PPARγ)、前脂肪细胞因子-1(Pref-1)以及线粒体解偶联蛋白1(UCP 1)、PR结构域蛋白16(PRDM 16)、跨膜蛋白26(TMEM 26)的mRNA水平无影响。DNJ诱导3 T3-L1前体脂肪细胞分化后,aP 2、PPARγ和Pref-1的表达明显降低,UCP 1、PRDM 16和TMEM 26的表达明显上调,脂质沉积减少。DNJ(10 μM)处理10 d后,p-AMPK/AMPK比值明显升高,DNJ对p-AMPK/AMPK、UCP 1和PRDM 16的影响可被AMPK抑制剂Compound C阻断。上述结果表明,降血糖药物DNJ可抑制白色前脂肪细胞分化过程中的脂肪生成,并通过激活AMPK促进白色前脂肪细胞向米色脂肪细胞转化,为解释DNJ对肥胖相关疾病的治疗作用提供了新的机制。
Obesity is a serious health challenge in the world, and searching effective drugs to cure obesity is of great importance. 1-Deoxynojirimycin (DNJ) is extracted from mulberry leaves and acts as an α-glucosidase inhibitor to lower blood glucose. Recent studies demonstrated that it also has anti-obesity effect, but the mechanisms remain unknown. In our present study, we mainly examined the effects of DNJ on beige remodeling of 3T3-L1 preadipocytes. We observed that DNJ didn't affect the mRNA levels of fatty acid binding protein 4 (aP2), peroxisome proliferator-activated receptor γ (PPARγ), preadipocyte factor-1 (Pref-1) as well as the mitochondrial uncoupling protein 1 (UCP1), PR domain containing protein 16 (PRDM16), transmembrane protein 26 (TMEM26) in undifferentiated preadipocytes. But after inducing 3T3-L1 preadipocytes to differentiation with white or beige adipogenic medium, DNJ significantly reduced aP2, PPARγ and Pref-1 expressions, while up-regulated the expressions of UCP1, PRDM16 and TMEM26, accompanying with decreased lipid deposition. The ratio of p-AMPK/AMPK was up-regulated by DNJ (10 μM) treatment for 10 days, and the effects of DNJ on p-AMPK/AMPK, UCP1 and PRDM16 could be blocked by AMPK inhibitor Compound C. These results demonstrated that hypoglycemic agent DNJ could suppress the adipogenesis during the differentiation of white preadipocytes, and promote the switch of white preadipocytes to beige adipocytes via activating AMPK, which provided new mechanisms for explaining the benefits of DNJ on obesity-related disorders.
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