Induction of hepatic insulin-like growth factor binding protein-1 (IGFBP-1) in rats by dietary n-6 polyunsaturated fatty acids.

A. Ghoshal, Z. Xu, G. Wood, M. C. Archer
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引用次数: 3

Abstract

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.
n-6多不饱和脂肪酸对肝脏胰岛素样生长因子结合蛋白1 (IGFBP-1)的诱导作用
胰岛素样生长因子(IGFs)是一种有丝分裂多肽,与多种正常生理过程以及肿瘤发生有关。IGF系统中一些成分的过度表达与人类和啮齿动物的肝癌发生有关。在大鼠肝脏中,富含n-6多不饱和脂肪酸(PUFA)的饮食可促进肿瘤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肝脏中IGF系统各组成部分表达的影响。饲粮中玉米油含量为20%的大鼠与饲粮中玉米油含量为5%的大鼠肝脏中IGF-1和1型受体的mRNA水平无显著差异。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)水平随饲粮中脂肪含量和类型的不同而改变。饲粮添加20%玉米油后1周内,IGFBP-1 mRNA的诱导量为5% CO组的2.5倍,1个月后进一步增加至6倍以上。此外,IGFBP-1蛋白仅在饲喂20% CO饲料的动物肝脏中检测到。在喂食含有红花(富含n-6 PUFAs)的高脂肪饮食的大鼠中,与喂食含有鲱鱼油(富含n-3 PUFAs)的高脂肪饮食的大鼠相比,IGFBP-1 mRNA的诱导量也增加了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生无关。由于IGFBP-1 mRNA在再生肝脏中上调,我们推断IGFBP-1 mRNA的诱导可能与细胞增殖的增加有关;然而,喂食20%一氧化碳的大鼠与喂食5%一氧化碳的大鼠的肝脏标记指数没有差异。总之,这些研究表明,饮食中的n-6 PUFAs显著诱导肝脏IGFBP-1,这是一种与肝癌发展有关的蛋白质。
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