The Effect of High-Fat Diet Feeding and Associated Transcriptome Changes in the Peak Lactation Mammary Gland in C57BL/6 Dams.

Maternal consumption of a high fat diet (HFD) during pregnancy has established adverse effects on the developing neonate. In this study, we aimedto investigate the effect of a HFD on the murine mammary gland during mid-lactation. Female C57BL/6J mice were placed on either a low-fat diet (LFD/10% fat) or HFD (60% fat) from three weeks of age through peak lactation (lactation day 11/L11). After four weeks of consuming either the LFD or HFD, female mice were bred. There were no significant differences in milk yield between treatment groups, which was measured from L1-L9. On L10, mice were subjected to an overnight fast and then euthanized on the morning of L11. Total RNA was isolated from inguinal mammary glands for whole transcriptome sequencing. Six hundred and twenty-eight genes were differentially expressed between the treatment groups. Notably, HFD feeding resulted in expression alterations of genes involved in collagen and cytoplasmic components. Additionally, genes related to inflammatory and immune responses were also impacted.Differential expression in gene transcript isoforms between the treatment groups was detected in three genes related to mammary duct development. This study sheds light as to how a HFD may affect the mammary gland transcriptomeduring mid-lactation.