Studies on the gene expression and physiological roles of cellular retinol-binding protein, type II in small intestine

1)我们研究了膳食脂肪酸调节小肠细胞视黄醇结合蛋白II(CRBP(II))基因表达的机制。与CRBP(II)基因启动子上的核受体反应元件结合的核蛋白(包括PPAR-RXR异源二聚体)的数量增加。饲料脂肪降低了小肠中PPAR亚型(PPARDelta)的mRNA水平。参与花生四烯酸代谢的酶的抑制剂不影响饮食脂肪诱导的CRBP(II)基因表达的增加。2)大鼠小肠组织中CRBP(II)和L型脂肪酸结合蛋白(L-FABP)的基因表达呈现协同的日变化。3)饥饿对大鼠空肠CRBP(II)、L-FABP和I-FABP基因表达的影响。这三个基因的mRNA水平在饥饿的第1天平行下降，但在饥饿的第3天上升到非饥饿对照水平以上。这些变化与空肠组织中三酰甘油含量的变化相对应，并可能反映了进入空肠细胞的脂肪酸的数量。4)给大鼠喂食过量的β-胡萝卜素，提高了空肠中的β-胡萝卜素裂解酶活性，而导致空肠中视网膜还原酶的活性下降。这一结果表明，过量摄入饮食中的β-胡萝卜素会下调视网膜向视黄醇的转化。

1) We investigated the mechanism whereby dietary fatty acids modulate the gene expression of cellular retinol-binding protein, type II (CRBP(II)) in the small intestine. The rats fed the high-fat diet showed a parallel increase in the transcription of CRBP(II) gene and the level of PPAROalpha mRNA, which was accompanied by an increase in the amount of nuclear proteins (including PPAR-RXR heterodimer) binding to the nuclear receptor-response elements located in the promoter of CRBP(II) gene. The mRNA level of a PPAR subtype (PPARdelta) was reduced in the small intestine by dietary fat. Inhibitors of enzymes involved in arachidonic acid metabolism did not influence the dietary fat- induced increase in the CRBP(II) gene expression. Transfection experiments revealed that CRBP(II) gene expression is induced by fatty acids through activation of PPAR-RXR heterodimer.2) Gene expressions of CRBP(II) and L-type fatty acid-binding protein (L-FABP) exhibited a coordinated diurnal variation in rat small intestine. Both CRBP(II) and L-FABP mRNA levels were elevated at feeding periods, attributable to the dietary fat-induced increase in the transcription of these two genes.3) Effects of starvation on the mRNA levels of CRBP(II), L-FABP and I-FABP were investigated in rat jejunum. The mRNA levels of these three genes decreased in parallel on day 1, but increased above the non- starved control level on day 3 of starvation. These variations corresponded with the changes in the amount of triacylglycerols in jejunal tissue, and may have reflected the amount of fatty acids coming into the enterocytes.4) Feeding excessive beta-carotene to rats enhanced the beta-carotene cleavage enzyme activity in the jejunum, while it caused a decrease in retinal reductase activity in the jejunum. This result suggests that the conversion of retinal to retinol is down-regulated by excesive intake of dietary beta-carotene.