Bovine milk consumption affects the transcriptome of porcine adipose stem cells: Do exosomes play any role?

The potential association of milk with childhood obesity has been widely debated and researched. Milk is known to contain many bioactive compounds as well as bovine exosomes rich in micro-RNA (miR) that can have effects on various cells, including stem cells. Among them, adipose stem cells (ASC) are particularly interesting due to their role in adipose tissue growth and, thus, obesity. The objective of this study was to evaluate the effect of milk consumption on miR present in circulating exosomes and the transcriptome of ASC in piglets. Piglets were supplemented for 11 weeks with 750 mL of whole milk (n = 6; M) or an isocaloric maltodextrin solution (n = 6; C). After euthanasia, ASC were isolated, quantified, and characterized. RNA was extracted from passage 1 ASC and sequenced. Exosomes were isolated and quantified from the milk and plasma of the pigs at 6-8 hours after milk consumption, and miRs were isolated from exosomes and sequenced. The transfer of exosomes from milk to porcine plasma was assessed by measuring bovine milk-specific miRs and mRNA in exosomes isolated from the plasma of 3 piglets during the first 6h after milk consumption. We observed a higher proportion of exosomes in the 80 nM diameter, enriched in milk, in M vs. C pigs. Over 500 genes were differentially expressed (DEG) in ASC isolated from M vs. C pigs. Bioinformatic analysis of DEG indicated an inhibition of the immune, neuronal, and endocrine systems and insulin-related pathways in ASC of milk-fed pigs compared with maltodextrin-fed pigs. Of the 900 identified miRs in porcine plasma exosomes, only 3 miRs were differentially abundant between the two groups and could target genes associated with neuronal functions. We could not detect exosomal miRs or mRNA transfer from milk to porcine-circulating plasma exosomes. Our data highlights the significant nutrigenomic role of milk consumption on ASC, a finding that does not appear to be attributed to miRs in bovine milk exosomes. The downregulation of insulin resistance and inflammatory-related pathways in the ASC of milk-fed pigs should be further explored in relation to milk and human health. In conclusion, the bioinformatic analyses and the absence of bovine exosomal miRs in porcine plasma suggest that miRs are not vertically transferred from milk exosomes.