Dietary polyunsaturated fats regulate rat liver sterol regulatory element binding proteins-1 and-2 in three distinct stages and by different mechanisms
Dietary polyunsaturated fats regulate rat liver sterol regulatory element binding proteins-1 and-2 in three distinct stages and by different mechanisms
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DOI：
10.1093/jn/132.11.3333
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发表时间：
2002-11-01
影响因子：
4.2
通讯作者：
Clarke, SD
中科院分区：
文献类型：
--
作者：
Xu, J;Cho, H;Clarke, SD
雄性Sprague-Dawley大鼠，训练消耗他们的日常能量需要在一个单一的3小时餐（0900-1200小时），被用来检查的假设，即多不饱和脂肪酸（PUFA）降低核含量的固醇调节元件结合蛋白（SREBP）-1和/或-2通过抑制蛋白水解释放成熟SREBP从膜锚定的前体池。在食用单次补充PUFA的膳食（即，10 g鱼油/100 g无脂饮食）的大鼠中的显著性高于仅饲喂无脂饮食的大鼠。SREBP-1和SREBP-2靶基因、脂肪酸合成酶和HMG-CoA合成酶的表达分别降低了63%和52%，但由膳食摄入引起的前体SREBP-1和SREBP-2的量显著增加不受影响。在食用第二餐鱼油后，成熟SREBP-1的核水平仅为喂食无脂饮食的大鼠的16%，但核SREBP-2的量与喂食无脂饮食的大鼠的水平没有差异。同样，SREBP-1和SREBP-2前体库的大小没有减少。直到大鼠食用5餐鱼油后，前体SREBP-1的肝脏浓度才出现下降。在这一点上，在喂食鱼油或红花油的大鼠中，SREBP-2的核含量实际上高出两倍（P < 0.05），但前体SREBP-2的量不受影响。这些数据表明，PUFA抑制SREBP-1和-2的体内蛋白水解释放，但对SREBP-2的影响是暂时的，可能反映了PUFA通过胆汁酸合成增强胆固醇损失的能力。
Male Sprague-Dawley rats, trained to consume their daily energy needs in a single 3-h meal (0900-1200 h), were used to examine the hypothesis that polyunsaturated fatty acids (PUFA) lowered the nuclear content of sterol regulatory element binding protein (SREBP)-1 and/or -2 by suppressing the proteolytic release of mature SREBP from the membrane-anchored precursor pool. The nuclear concentrations of hepatic SREBP-1 and -2 were 50 and 42% lower (P < 0.05) in rats that consumed a single PUFA-supplemented meal (i.e., 10 g fish oil/100 g fat-free diet) than in rats fed the fat-free diet alone. This was paralleled by 63 and 52% reductions in the expression of the SREBP-1 and -2 target genes, fatty acid synthase and HMG-CoA synthase, respectively; but the marked increase in the amount of precursor SREBP-1 and -2 resulting from meal ingestion was unaffected. After the consumption of a second meal of fish oil, the nuclear level of mature SREBP-1 was only 16% of that in rats fed the fat-free diet, but the amount of nuclear SREBP-2 was not different from the level in rats fed the fat-free diet. Again, the sizes of the SREBP-1 and -2 precursor pools were not reduced. A decrease in the hepatic concentration of precursor SREBP-1 did not occur until rats had consumed 5 meals of fish oil. At this point, the nuclear content of SREBP-2 was actually twofold higher (P < 0.05) in rats fed fish oil or safflower oil, but the amount of precursor SREBP-2 was unaffected. These data indicate that PUFA suppress the in vivo proteolytic release of SREBP-1 and -2, but the effect on SREBP-2 is transitory, possibly reflecting the ability of PUFA to enhance cholesterol losses via bile acid synthesis.