Comparative study of sesame lignans affecting gene expression profile and fatty acid oxidation in rat liver

The impact of sesamin, episesamin and sesamolin (sesame lignans) on hepatic gene expression profiles was compared with a DNA microarray. Male Sprague-Dawley rats were fed experimental diets containing 0.2% sesamin, episesamin or sesamolin, and a control diet free of lignans for 15 d. Compared to a lignan-free diet, a diet containing sesamin, episesamin and sesamolin caused 1.5- and 2-fold changes in the expression of 128 and 40, 526 and 152, and 516 and 140 genes, respectively. The lignans modified not only the mRNA levels of many enzymes involved in hepatic fatty acid oxidation, but also those of proteins involved in the transportation of fatty acids into hepatocytes and their organelles, and regulate hepatic concentrations of carnitine, CoA and malonyl-CoA. It is apparent that sesame lignans stimulate hepatic fatty acid oxidation by affecting the gene expression of various proteins regulating hepatic fatty acid metabolism. We also observed that lignans modified the gene expression of various proteins involved in hepatic lipogenesis, cholesterogenesis and glucose metabolism. The changes were generally greater with episesamin and sesamolin than with sesamin. In terms of the amounts accumulated in serum and the liver, the lignans ranked in the order sesamolin, episesamin and sesamin. The differences in bio-availability among these lignans appear to be important to their divergent physiological activities.本研究采用DNA微阵列（DNA microarray）技术，比较了芝麻木脂素（sesame lignans）中的芝麻素（sesamin）、表芝麻素（episesamin）与芝麻林素（sesamolin）对肝脏基因表达谱的影响。实验选用雄性斯普拉-道来大鼠（Sprague-Dawley rats），分别饲喂添加0.2%芝麻素、0.2%表芝麻素、0.2%芝麻林素的实验日粮，以及不含木脂素的对照日粮，连续干预15天。 相较于无木脂素日粮，添加芝麻素、表芝麻素、芝麻林素的日粮分别使128个、526个、516个基因的表达发生1.5倍变化，同时使40个、152个、140个基因的表达发生2倍变化。上述芝麻木脂素不仅可调控参与肝脏脂肪酸氧化的多种酶的mRNA水平，还可调控负责脂肪酸向肝细胞及其细胞器转运的相关蛋白的mRNA水平，并调节肝脏内肉碱、辅酶A（CoA）以及丙二酰辅酶A（malonyl-CoA）的浓度。 由此可见，芝麻木脂素可通过调控参与肝脏脂肪酸代谢的多种蛋白的基因表达，促进肝脏脂肪酸氧化过程。本研究同时观察到，芝麻木脂素还可调控参与肝脏脂肪生成、胆固醇合成以及葡萄糖代谢的多种蛋白的基因表达。整体而言，表芝麻素与芝麻林素诱导的基因表达变化幅度均大于芝麻素。就血清与肝脏中的蓄积量而言，三种木脂素的排序为芝麻林素＞表芝麻素＞芝麻素。上述三种木脂素在生物利用度（bioavailability）上的差异，或是导致其生理活性存在差异的重要原因。