Ghoshal A K, Xu Z, Wood G A, Archer M C
Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada M5S 3E2.
Proc Soc Exp Biol Med. 2000 Nov;225(2):128-35. doi: 10.1046/j.1525-1373.2000.22516.x.
The insulin-like growth factors (IGFs) are mitogenic polypeptides that have been linked to a variety of normal physiological processes as well as neoplasia. Overexpression of several components of the IGF system is associated with hepatocarcinogenesis in humans and rodents. In rat liver, diets rich in n-6 polyunsaturated fatty acid (PUFA) enhance the development of preneoplastic lesions and tumors. Therefore, the objective of this study was to determine the effect of these dietary fatty acids on the hepatic expression of the various components of the IGF system. The mRNA levels of IGF-1 and the type 1 receptor were not different in livers of rats fed a diet containing 20% corn oil (CO) compared with those fed 5% CO. Analysis of the IGF binding proteins revealed that insulin-like growth factor binding protein-1 (IGFBP-1) levels were altered by the amount and type of dietary fat. A 2.5-fold induction of IGFBP-1 mRNA occurred within 1 week after the animals were fed the 20% corn oil diet compared with those fed 5% CO and was further enhanced to over 6-fold after 1 month. Furthermore, IGFBP-1 protein was only detectable in the livers of animals fed the 20% CO diet. Induction of IGFBP-1 mRNA (4.5-fold) also occurred in rats fed a high-fat diet containing safflower (rich in n-6 PUFAs) compared with those fed a high-fat diet containing menhaden oil (rich in n-3 PUFAs). The induction of IGFBP-1 mRNA was independent of serum insulin levels and the development of insulin resistance. Since IGFBP-1 mRNA is upregulated in regenerating liver, we reasoned that the induction of IGFBP-1 mRNA may be associated with an increase in cell proliferation; however, no difference was observed in the hepatic labeling index of rats fed the 20% CO compared with the 5% CO diet. In summary, these studies show a striking induction by dietary n-6 PUFAs of hepatic IGFBP-1, a protein that has been implicated in liver cancer development.
胰岛素样生长因子（IGFs）是促有丝分裂多肽，与多种正常生理过程以及肿瘤形成有关。IGF系统的几个组分的过表达与人类和啮齿动物的肝癌发生相关。在大鼠肝脏中，富含n-6多不饱和脂肪酸（PUFA）的饮食会促进癌前病变和肿瘤的发展。因此，本研究的目的是确定这些膳食脂肪酸对IGF系统各组分肝脏表达的影响。与喂食5%玉米油（CO）的大鼠相比，喂食含20%玉米油饮食的大鼠肝脏中IGF-1和1型受体的mRNA水平没有差异。对IGF结合蛋白的分析表明，胰岛素样生长因子结合蛋白-1（IGFBP-1）水平会因膳食脂肪的量和类型而改变。与喂食5%CO的大鼠相比，动物喂食20%玉米油饮食1周后，IGFBP-1 mRNA诱导增加了2.5倍，1个月后进一步增加至超过6倍。此外，仅在喂食20%CO饮食的动物肝脏中可检测到IGFBP-1蛋白。与喂食含鲱鱼油（富含n-3 PUFAs）的高脂饮食的大鼠相比，喂食含红花油（富含n-6 PUFAs）的高脂饮食的大鼠也出现了IGFBP-1 mRNA的诱导（4.5倍）。IGFBP-1 mRNA的诱导与血清胰岛素水平和胰岛素抵抗的发展无关。由于IGFBP-1 mRNA在再生肝脏中上调，我们推测IGFBP-1 mRNA的诱导可能与细胞增殖增加有关；然而，与喂食5%CO饮食的大鼠相比，喂食20%CO饮食的大鼠肝脏标记指数没有差异。总之，这些研究表明膳食n-6 PUFAs对肝脏IGFBP-1有显著诱导作用，IGFBP-1是一种与肝癌发展有关的蛋白质。
