Department of Pathobiochemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
Department of Medicinal Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
Molecules. 2019 Apr 28;24(9):1668. doi: 10.3390/molecules24091668.
Limonoids are phytochemicals with a variety of biological properties. In the present study, we elucidated the molecular mechanism of suppression of adipogenesis in adipocytes by a limonoid, 7-deacetoxy-7-oxogedunin (CG-1) from (Meliaceae), known as andiroba. CG-1 reduced the accumulation of intracellular triglycerides in a concentration-dependent manner. The expression levels of the adipogenic, lipogenic, and lipolytic genes were decreased by CG-1 treatment, whereas the glycerol release level was not affected. When CG-1 was added into the medium during days 0-2 of 6-days-adipogenesis, the accumulation of intracellular lipids and the mRNA levels of the adipogenesis-related genes were decreased. In addition, the phosphorylation level of insulin receptor substrate-1 (IRS-1) and Akt in the early phase of adipocyte differentiation (within 1 day after initiating adipocyte differentiation) was reduced by CG-1. Furthermore, insulin-activated translocation of glucose transporter 4 to the plasma membranes in adipocytes was suppressed by CG-1, followed by decreased glucose uptake into the cells. These results indicate that an andiroba limonoid CG-1 suppressed the accumulation of intracellular lipids in the early phase of adipocyte differentiation through repression of IRS-1/Akt-mediated glucose uptake in adipocytes.
柠檬苦素是具有多种生物学特性的植物化学物质。在本研究中，我们阐明了从楝科植物 known as andiroba 的一种柠檬苦素 7-脱乙酰氧基-7-氧代格尔德酮（CG-1）抑制脂肪细胞脂肪生成的分子机制。CG-1 以浓度依赖的方式减少细胞内甘油三酯的积累。CG-1 处理后，脂肪生成、脂肪生成和脂肪分解基因的表达水平降低，而甘油释放水平不受影响。当 CG-1 在 6 天脂肪生成过程的第 0-2 天添加到培养基中时，细胞内脂质的积累和与脂肪生成相关的基因的 mRNA 水平降低。此外，CG-1 还降低了脂肪细胞分化早期（脂肪细胞分化开始后 1 天内）胰岛素受体底物 1（IRS-1）和 Akt 的磷酸化水平。此外，CG-1 抑制了胰岛素激活的葡萄糖转运蛋白 4 向脂肪细胞膜的易位，随后减少了细胞内的葡萄糖摄取。这些结果表明，一种来自安第罗巴的柠檬苦素 CG-1 通过抑制 IRS-1/Akt 介导的脂肪细胞中葡萄糖摄取，抑制了脂肪细胞分化早期细胞内脂质的积累。
