Effect of high-fat diet on secreted milk transcriptome in midlactation mice

Abstract

High-fat diet (HFD) during lactation alters milk composition and is associated with development of metabolic diseases in the offspring. We hypothesized that HFD affects milk microRNA (miRNA) and mRNA content, which potentially impact offspring development. Our objective was to determine the effect of maternal HFD on secreted milk transcriptome. To meet this objective, 4 wk old female ICR mice were divided into two treatments: control diet containing 10% kcal fat and HFD containing 60% kcal fat. After 4 wk on CD or HFD, mice were bred while continuously fed the same diets. On postnatal day 2 (P2), litters were normalized to 10 pups, and half the pups in each litter were cross-fostered between treatments. Milk was collected from dams on P10 and P12. Total RNA was isolated from milk fat fraction of P10 samples and used for mRNA-Seq and small RNA-Seq. P12 milk was used to determine macronutrient composition. After 4 wk of prepregnancy feeding HFD mice weighed significantly more than did the control mice. Lactose and fat concentration were significantly ( P < 0.05) higher in milk of HFD dams. Pup weight was significantly greater ( P < 0.05) in groups suckled by HFD vs. control dams. There were 25 miRNA and over 1,500 mRNA differentially expressed (DE) in milk of HFD vs. control dams. DE mRNA and target genes of DE miRNA enriched categories that were primarily related to multicellular organismal development. Maternal HFD impacts mRNA and miRNA content of milk, if bioactive nucleic acids are absorbed by neonate differences may affect development.

Effect of high-fat diet feeding and associated transcriptome changes in the peak lactation mammary gland in C57BL/6 dams

“…GO term analysis indicates that these genes were enriched in plasma membrane parts (P value Ͻ 0.001), with Cd14 as the hub gene. In contrast to the work by Chen et al (14), where the authors identified casein genes as the most abundantly expressed mRNAs, we identified no shared genes when comparing the list of DEGs in this study to the top 50 most significantly differentially expressed genes in the milk transcriptome study by Chen et al Out of the list of 1,572 differentially expressed mRNA genes reported by Chen and coauthors, only 21 of them were identified in our study, indicating the unique transcriptome profiles in mammary gland and milk samples during midlactation. Among these, 10 of them showed the same trend of upregulation in our study.…”

“…Significant DEGs in our study were compared with the results of previously published work regarding the effect of HFD (from puberty through midlactation) on the murine midlactation milk transcriptome (14). Specifically, we compared our list of DEGs with the top 50 most significant DEGs of the milk transcriptome as well as the complete list of DEGs reported by Chen et al (14). The top 1% of most abundantly expressed genes identified in our study were also compared with these most highly expressed genes reported by this group.…”

“…Some studies have shown transcriptomic changes in milk or mammary gland in animal models fed an HFD (20,64). A recent study found that mice fed an HFD before and during lactation have significantly altered microRNA expression lev-els as well as whole transcriptome changes in milk (14). Our study is unique in that it is one of the few studies that examine the effect of an HFD on the transcriptomics of the peaklactation murine mammary gland when the dam is administered a given diet from weaning (puberty) through lactation.…”

Milk MicroRNAs in Health and Disease

“…In mice, high‐fat diet (HFD) changed microRNA secretion in milk. Notably, development‐associated miR‐142a‐5p, miR‐223‐5p, miR‐10b‐5p, miR‐142a‐3p, and miR‐466d‐3p were differentially impacted by HFD (Chen et al., ). Therefore, dietary patterns in the mothers might impact the microRNA profile, possibly allowing for diagnosis of dietary deviation (for example, malnutrition) or, in the case of microRNA transfer to the infant (Melnik & Schmitz, , ; Zempleni et al., ), altering the potential outcome of milk microRNAs bioactivity.…”

Invited review: MicroRNAs in bovine colostrum—Focus on their origin and potential health benefits for the calf

“…Women who consume a diet rich in fat (30% carbohydrate, 55% fat, and 15% protein) showed increased expression of miR-67 and miR-27 in their milk fat globules compared with women on an high-carbohydrate diet (60% carbohydrate, 25% fat, and 15% protein; Munch et al, 2013). Mice that received a diet rich in fat (5.24 kcal/g), showed 25 DE miRNAs compared with mice fed a control diet (3.85 kcal/g; Chen et al, 2017). When cows were fed a diet supplemented with 5% safflower or linseed oil, 22 and 14 miRNAs (7 in common), respec- tively, were differentially expressed in the mammary gland (Li et al, 2015).…”