Kaempferol Isolated from Nelumbo nucifera Inhibits Lipid Accumulation and Increases Fatty Acid Oxidation Signaling in Adipocytes
Kaempferol Isolated from Nelumbo nucifera Inhibits Lipid Accumulation and Increases Fatty Acid Oxidation Signaling in Adipocytes
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DOI：
10.1089/jmf.2015.3457
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发表时间：
2015-12-01
影响因子：
2.4
通讯作者：
Kim, Hyeung-Rak
中科院分区：
文献类型：
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作者：
Lee, Bonggi;Kwon, Misung;Kim, Hyeung-Rak
莲的雄蕊由于其抗氧化、降血糖和抗动脉粥样硬化活性而被用作中药。而N. nucifera，对肥胖的影响还不完全清楚。我们研究了山奈酚对3 T3-L1脂肪细胞脂肪生成和脂肪酸氧化信号通路的影响。在脂肪细胞分化过程中，山奈酚以剂量和时间依赖性方式减少细胞质甘油三酯（TG）的积累。TG的积累迅速逆转恢复山奈酚治疗。山奈酚广泛降低成脂转录因子及其与脂质积聚相关的靶基因的mRNA或蛋白质水平。山奈酚还抑制脂肪细胞的葡萄糖摄取和葡萄糖转运蛋白GLUT 4 mRNA的表达。此外，蛋白质对接模拟表明，山奈酚可以通过与过氧化物酶体增殖物激活受体（PPAR）α的VAL 324、THR 279和LEU 321残基形成疏水相互作用，直接结合并激活PPARα。结合亲和力高于已知的PPARα激动剂非诺贝特。结果表明，PPARα靶基因mRNA表达水平升高。我们的研究表明，山奈酚在抑制脂肪生成转录因子和脂质积累的同时，可能与PPARα结合并刺激脂肪细胞中的脂肪酸氧化信号。
Stamens ofNelumbo nuciferaGaertn have been used as a Chinese medicine due to its antioxidant, hypoglycemic, and antiatherogenic activity. However, the effects of kaempferol, a main component ofN. nucifera, on obesity are not fully understood. We examined the effect of kaempferol on adipogenesis and fatty acid oxidation signaling pathways in 3T3-L1 adipocytes. Kaempferol reduced cytoplasmic triglyceride (TG) accumulation in dose and time-dependent manners during adipocyte differentiation. Accumulation of TG was rapidly reversed by retrieving kaempferol treatment. Kaempferol broadly decreased mRNA or protein levels of adipogenic transcription factors and their target genes related to lipid accumulation. Kaempferol also suppressed glucose uptake and glucose transporter GLUT4 mRNA expression in adipocytes. Furthermore, protein docking simulation suggests that Kaempferol can directly bind to and activate peroxisome proliferator-activated receptor (PPAR)-αby forming hydrophobic interactions with VAL324, THR279, and LEU321 residues of PPARα. The binding affinity was higher than a well-known PPARαagonist fenofibrate. Consistently, mRNA expression levels of PPARαtarget genes were increased. Our study indicates while kaempferol inhibits lipogenic transcription factors and lipid accumulation, it may bind to PPARαand stimulate fatty acid oxidation signaling in adipocytes.