The Effect of High Fat Diet on Secreted Milk Transcriptome in Mid-Lactation Mice

Yulu Chen, Purdue University


Milk is the only source of nutrition for the suckling neonate. Epidemiological and controlled animal studies report that early exposure to maternal high-fat diet during pregnancy and lactation has long-term effects on offspring health, which include development of metabolic syndrome, hypertension, type 2 diabetes, and obesity. Cross-fostering studies in rodents showed when pups are exposed to maternal high-fat diet only during lactation they develop a metabolic-like syndrome as adults, indicating that milk alone has long-term programming effects on offspring development. Breast milk is not only a source of nutrition for the suckling neonate, but also contains bioactive molecules, such as growth factors and immune factor, that affect the offspring’s development. Milk composition changes when maternal diet is changed. Changes in fat composition of maternal diet not only change the nutrient content of milk, but also components that have potential bioactivity. Recently developed highly sensitive high-throughput analysis tools have led to the discovery of molecules that may have bioactive effects on offspring development. Among the emerging discoveries is the abundance of nucleic acids in milk, including microRNAs (miRNAs). MiRNAs are small non-coding RNA, which are around 22 nucleotides long. The function of miRNAs is to silence message RNA (mRNA) expression. Silencing is accomplished through post-transcriptional regulation of gene expression. MiRNAs play a major role in a large range of biological processes, including regulation of cell death, cell proliferation, cell differentiation, metabolism, and patterning of nervous system. MiRNAs are not only found inside cells, but also have the ability to exist extracellularly. Extracellular miRNAs have been isolated from cell culture media, blood, saliva, tears, urine, and milk. MiRNAs in milk are found packaged in somatic cells, exosomes and other microvesicles, which are hypothesized to function to transfer biologically active miRNA from the mother to the infant. Several studies support that miRNA content in breast milk can be affected by diet and disease. The aim of this work was to use RNA-seq high-throughput technology to generate a comprehensive transcriptome miRNA and gene coding messenger RNA in mouse milk. Secondly, to determine the effect of maternal high fat diet on secreted milk transcriptome. The RNA-seq results in our study showed that high-fat diet during lactation impacts secreted milk miRNA and mRNA composition. Interestingly, miRNA and mRNA differentially expressed (DE) in milk from high fat versus control fed dams targeted nervous system development. These findings suggest there is a potential that miRNAs and mRNAs in milk target neonate.




Casey, Purdue University.

Subject Area

Animal sciences

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