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

The insulin-like growth factors (IGFs) are mitogenic polypeptides that have been linked to a variety of normal physiological processes as well as neop lasia, 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 preneop lastic lesions and tumors. Therefore, the objective of this study was to de termine the effect of these dietary fatty acids on the hepatic expression o f the various components of the IGF system. The mRNA levels of IGF-1 and th e type 1 receptor were not different in livers of rats fed a diet containin g 20% corn oil (CO) compared with those fed 5% CO, Analysis of the IGF bind ing proteins revealed that insulin-like growth factor binding protein-1 (IG FBP-1) levels were altered by the amount and type of dietary fat, A 2.5-fol d induction of IGFBP-1 mRNA occurred within 1 week after the animals were f ed the 20% corn oil diet compared with those fed 5% CO and was further enha nced to over 6-fold after 1 month. Furthermore, IGFBP-1 protein was only de tectable 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 safflo wer (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 indepen dent of serum insulin levels and the development of insulin resistance, Sin ce 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 prolif eration; 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 stud ies show a striking induction by dietary n-6 PUFAs of hepatic IGFBP-1, a pr otein that has been implicated in liver cancer development.