OM2, a Novel Oligomannuronate-Chromium(III) Complex, Promotes Mitochondrial Biogenesis and Lipid Metabolism in 3T3-L1 Adipocytes via the AMPK-PGC1α Pathway.
OM2, a Novel Oligomannuronate-Chromium(III) Complex, Promotes Mitochondrial Biogenesis and Lipid Metabolism in 3T3-L1 Adipocytes via the AMPK-PGC1α Pathway.
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OM2 是一种新型寡甘露糖醛酸铬 (III) 复合物，通过 AMPK-PGC1 α 途径促进 3T3-L1 脂肪细胞中的线粒体生物合成和脂质代谢
DOI：
10.1371/journal.pone.0131930
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Yu G
中科院分区：
文献类型：
--
作者：
Hao J;Hao C;Zhang L;Liu X;Zhou X;Dun Y;Li H;Li G;Zhao X;An Y;Liu J;Yu G
在我们以前的研究中，我们从海洋藻酸盐中制备了新的寡甘露糖醛酸-铬（III）络合物（OM 2，OM 4），并发现这些化合物在C2 C12骨骼肌细胞中比寡甘露糖醛酸（OM），铬和二甲双胍更能敏化胰岛素作用。在本研究中，我们研究了它们对分化的3 T3-L1脂肪细胞的线粒体生物合成、脂质代谢以及潜在的分子机制的影响。我们首先利用pGL 3-PGC 1 α和pGL 3-ATGL启动子质粒比较了它们对PGC 1 α和ATGL转录活性的影响。然后通过透射电子显微镜和MitoTracker染色定量线粒体生物合成。线粒体耗氧量和脂肪酸氧化通过氧生物传感器系统和氚标记水闪烁测量。实时荧光定量PCR检测线粒体DNA和线粒体生物合成及脂质氧化相关基因的表达。AMPK与其他蛋白质表达水平通过蛋白质印迹法测量。用化合物C和PGC 1 α的siRNA抑制OM 2诱导的AMPK-PGC 1 α信号通路。我们发现OM 2刺激3 T3-L1脂肪细胞AMPK-PGC 1 α通路，这与诱导线粒体生物合成、改善线粒体功能、通过增强脂肪酸β-氧化和增加ATGL蛋白表达减少脂质积累有关。我们的数据表明，海洋寡糖衍生的OM 2可能代表一类新的分子，可能是有用的2型糖尿病的预防和治疗，通过上调AMPK-PGC 1 α信号通路。
In our previous studies, we prepared novel oligomannuronate-chromium(III) complexes (OM2, OM4) from marine alginate, and found that these compounds sensitize insulin action better than oligomannuronate(OM), chromium, and metformin in C2C12 skeletal muscle cells. In the present study, we studied their effects on mitochondrial biogenesis, lipid metabolism, and the underlying molecular mechanisms in differentiated 3T3-L1 adipocytes. We firstly used the pGL3-PGC1α and pGL3-ATGL promoter plasmids to compare their effects on PGC1α and ATGL transcription activities. Then mitochondrial biogenesis was quantified by transmission electron microscopy and MitoTracker staining. Mitochondrial oxygen consumption and fatty acid oxidation were measured by an oxygen biosensor system and ³H-labelled water scintillation. The mitochondrial DNA and mRNA involved in mitochondrial biogenesis and lipid oxidation were evaluated by real-time PCR. AMPK together with other protein expression levels were measured by western blotting. The inhibitor compound C and siRNA of PGC1α were used to inhibit the OM2-induced AMPK-PGC1α signaling pathway. And we found that OM2 stimulated AMPK-PGC1α pathway in the 3T3-L1 adipocytes, which were correlated with induced mitochondrial biogenesis, improved mitochondrial function, and reduced lipid accumulation by enhanced fatty acid β-oxidation and augmented ATGL protein expression. Our data indicated that the marine oligosaccharide-derived OM2 might represent a novel class of molecules that could be useful for type 2 diabetes prevention and treatment by up-regulating AMPK-PGC1α signaling pathway.