Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Science City, Guangzhou, P. R. China.
Mol Nutr Food Res. 2010 Mar;54(3):345-52. doi: 10.1002/mnfr.200900119.
Vitamin E is comprised of two classes of compounds: tocopherols and tocotrienols. Tocotrienol-enriched palm oil has been shown to help reduce blood glucose levels in patients and preclinical animal models. However, the mechanistic basis for tocotrienol action is not well established. Peroxisome proliferator-activated receptors alpha, gamma, and delta (PPARalpha, PPARgamma, and PPARdelta) are ligand-regulated transcription factors that play essential roles in energy metabolism. Importantly, synthetic PPARalpha and PPARgamma ligands are currently used for treating hyperlipidemia and diabetes. In this study, we present data that tocotrienols within palm oil functioned as PPAR modulators. Specifically, both alpha- and gamma-tocotrienol activated PPARalpha, while delta-tocotrienol activated PPARalpha, PPARgamma, and PPARdelta in reporter-based assays. Tocotrienols enhanced the interaction between the purified ligand-binding domain of PPARalpha with the receptor-interacting motif of coactivator PPARgamma coactivator-1alpha. In addition, the tocotrienol-rich fraction of palm oil improved whole body glucose utilization and insulin sensitivity of diabetic Db/Db mice by selectively regulating PPAR target genes. These lines of evidence collectively suggested that PPARs represent a set of molecular targets of tocotrienols.
维生素 E 由两类化合物组成：生育酚和三烯生育酚。富含三烯生育酚的棕榈油已被证明有助于降低患者和临床前动物模型的血糖水平。然而，三烯生育酚作用的机制基础尚未得到很好的确立。过氧化物酶体增殖物激活受体 α、γ 和 δ（PPARα、PPARγ 和 PPARδ）是配体调节的转录因子，在能量代谢中发挥着重要作用。重要的是，合成的 PPARα 和 PPARγ 配体目前用于治疗高脂血症和糖尿病。在这项研究中，我们提供了数据表明棕榈油中的三烯生育酚作为 PPAR 调节剂发挥作用。具体来说，α-和γ-三烯生育酚均可激活 PPARα，而δ-三烯生育酚可在基于报告的测定中激活 PPARα、PPARγ 和 PPARδ。三烯生育酚增强了纯化的 PPARα 配体结合域与辅激活因子 PPARγ 共激活因子 1α 的受体相互作用基序之间的相互作用。此外，富含三烯生育酚的棕榈油通过选择性调节 PPAR 靶基因改善了糖尿病 Db/Db 小鼠的全身葡萄糖利用和胰岛素敏感性。这些证据表明，PPAR 是三烯生育酚的一组分子靶标。
