Hashidume Tsutomu, Sasaki Takashi, Inoue Jun, Sato Ryuichiro
Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo.
Biosci Biotechnol Biochem. 2011;75(9):1702-7. doi: 10.1271/bbb.110224. Epub 2011 Sep 7.
We examined to determine whether hepatic gene expression is affected in mice in which blood lipid levels remain unchanged fed soy protein isolate (SPI) for a short time. We also examined SPI-mediated effects in farnesoid X receptor (FXR)-deficient mice. Compared with casein, SPI affected the expression of various hepatic genes related to lipid metabolism in the wild-type mice. No effects of SPI were observed in the FXR-deficient mice, suggesting the importance of FXR. Hepatic peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) gene expression was reduced by SPI, and this might be associated with a decrease in FXR expression. Decreased FXR led to decreased expression of its target, the bile-salt export pump necessary for bile acid secretion and dietary lipid absorption. The earliest response to SPI was a decrease in hepatic sterol regulatory element-binding protein (SREBP)-1c mRNA, on day 3. SPI activated hepatic adenosine monophosphate-activated protein kinase (AMPK), which can lead to a reduction in SREBP-1c mRNA. These data indicate the importance of SREBP-1c and PGC-1α/FXR in SPI-mediated alterations in hepatic gene expression.
我们进行了研究，以确定在短期喂食大豆分离蛋白（SPI）后血脂水平保持不变的小鼠中，肝脏基因表达是否受到影响。我们还研究了SPI在法尼醇X受体（FXR）缺陷小鼠中的介导作用。与酪蛋白相比，SPI影响了野生型小鼠中各种与脂质代谢相关的肝脏基因的表达。在FXR缺陷小鼠中未观察到SPI的作用，这表明FXR的重要性。SPI降低了肝脏过氧化物酶体增殖物激活受体γ共激活因子1α（PGC-1α）基因的表达，这可能与FXR表达的降低有关。FXR的降低导致其靶标——胆汁酸分泌和膳食脂质吸收所必需的胆盐输出泵的表达降低。对SPI的最早反应是在第3天肝脏固醇调节元件结合蛋白（SREBP）-1c mRNA减少。SPI激活了肝脏单磷酸腺苷激活蛋白激酶（AMPK），这可导致SREBP-1c mRNA减少。这些数据表明SREBP-1c和PGC-1α/FXR在SPI介导的肝脏基因表达改变中的重要性。
