Lipidomic fatty acid profile and global gene expression pattern in mammary gland of rats that were exposed to lard-based high fat diet during fetal and lactation periods associated to breast cancer risk in adulthood

Abstract

The persistent effects of animal fat consumption during pregnancy and nursing on the programming of breast cancer risk among female offspring were studied here. We have previously found that female offspring of rat dams that consumed a lard-based high-fat (HF) diet (60% fat-derived energy) during pregnancy, or during pregnancy and lactation, were at a reduced risk of developing mammary cancer. To better understand the unexpected protective effects of early life lard exposure, we have applied lipidomics and nutrigenomics approaches to investigate the fatty acid profile and global gene expression patterns in the mammary tissue of the female offspring. Consumption of this HF diet during gestation had few effects on the mammary tissue fatty acids profile of young adult offspring, while exposure from gestation throughout nursing promoted significant alterations in the fatty acids profile. Major differences were related to decreases in saturated fatty acids (SFA) and increases in omega-6 polyunsaturated fatty acids (PUFAs), monounsaturated fatty acids (MUFAs) and conjugated linolenic acid (CLA) concentrations. In addition several differences in gene expression patterns by microarray analysis between the control and in utero or in utero and during lactation HF exposed offspring were identified. Differential dependency network (DDN) analysis indicated that many of the genes exhibited unique connections to other genes only in the HF offspring. These unique connections included Hrh1-Ythdf1 and Repin1-Elavl2 in the in utero HF offspring, and Rnf213-Htr3b and Klf5-Chrna4 in the in utero and lactation HF offspring, compared with the control offspring. We conclude that an exposure to a lard-based HF diet during early life changes the fatty acid profile and transcriptional network in mammary gland in young adult rats, and these changes appear to be consistent with reduced mammary cancer risk observed in our previous study.

In utero exposure of rats to high-fat diets perturbs gene expression profiles and cancer susceptibility of prepubertal mammary glands

“…Recent work by Hilakivi-Clarke and associates [23] states that dietary and estrogenic exposures during pregnancy increase breast cancer risk in multiple generations of offspring, possibly through epigenetic mechanisms. The studies by Andrade et al [62, 63] showed exposure to a lard-based HF diet during early life changes the fatty acid profile and transcriptional network in mammary gland in young adult rats, which supports our findings that saturated butter fat, modifies the transcriptome and subsequent gene expression patterns. Another study by Pan et al [64] revealed maternal high fat exposure represses p16 (INK4a) gene expression in the mammary gland of offspring through changes of histone modifications and HDAC3 binding activity within the regulatory regions of the p16 (INK4a) gene.…”

Early Exposure to a High Fat/High Sugar Diet Increases the Mammary Stem Cell Compartment and Mammary Tumor Risk in Female Mice

“…Data are presented as mean AE SEM. ÃÃÃ , P < 0.001. significantly reduced tumor incidence and multiplicity (40), and their follow-up study shows that mammary tissues from these protected animals exhibit permanent changes in their fatty acid profiles and transcriptional networks (41). Therefore, this study brings additional insights into the impact of switching diets during early development.…”

The Mediterranean Diet and Breast Cancer: A Personalised Approach

“…Dietary exposure during foetal development is not the focus of this review. However, the authors refer the reader to a couple of informative articles focused on this topic [140,141].…”