Lipocalin-2 (Lcn2) expression is mediated by maternal nutrition during the development of the fetal liver

Abstract: The mechanisms by which maternal protein deficiency programs insulin action in the offspring are poorly understood. The interpretation of transcriptomics is complicated by homeostatic adaptations, for example, changes in amino acid metabolism, which are potentially unrelated to the programming mechanism. The fatty acid composition of the maternal diet modulates the programming of insulin action, offering a possible strategy to circumvent these complications. Fetal livers harvested on d21 of gestation from pregnant rats fed high-protein (18 % w/w) and low-protein (9 % w/w) diets prepared with either corn or soya oil were screened with rat genome microarrays. Although a low-protein maternal diet altered the abundance of more than one hundred mRNAs in the fetal liver, only 40 were changed by the fatty acid composition of the diet (P < 0.05). One of these mRNAs was identified as lipocalin-2 (Lcn2). This pattern of differential expression was confirmed by qRT-PCR. The expression of Lcn2 was decreased by low-protein diets when the diet contained soya oil, whereas the effect of protein was much smaller in the group fed diets prepared with corn oil. The decrease in Lcn2 expression produced by soya oil persisted into adult life. Levels of the Lcn2 protein were closely correlated to the mRNA abundance. The results suggest a possible involvement of Lcn2 in the programming of hepatic function.