Could lipocalin 2 be involved in the effects of iron overload and a high-fat diet on neuronal death? An exploratory study

Abstract

Abstract Lipocalin 2 (LCN2) controls iron levels, inflammation, cell death and is associated with neurodegenerative conditions. Moreover, obesity and insulin resistance modulate LCN2 expression. In this study we explored the effects of neonatal iron overload and a high-fat diet (HFD) after weaning on gene expression of LCN2, its receptor 24p3R, and the pro-apoptotic BCL-2-interacting mediator of cell death (BIM), besides evaluating the levels of LCN2 and of the anti-apoptotic protein B-cell lymphoma 2 (BCL2). Male Wistar rats received vehicle or carbonyl iron (30mg/kg) from the 12th to the 14th postnatal day. After weaning animals were treated with a HFD or a standard diet. At 9 months animal were euthanized and the hippocampus collected for RT-qPCR analysis of gene expression and Western Blot analysis of protein levels. The results indicate that iron overload during the neonatal period induced an increase in the gene expression for LCN2, its receptor 24p3R, and BIM, besides an increase of LCN2 protein levels. The exposure to a HFD throughout life, increased animals’ body weight and led to the decrease on BIM mRNA and BCl2 protein levels. Moreover, the combination of iron overload and HFD exacerbated the increase in LCN2 levels. In conclusion, the results of this study give support to the hypothesis that early life iron overload and a high fat diet are potential risk factors (each one alone and together) for neuronal death mediated by LCN2.