Dietary Depletion of Bovine Milk Exosomes Elicits Changes in Amino Acid Metabolism in C57BL/6 Mice

Abstract

BackgroundExosomes are small, cargo‐containing vesicles that are secreted by donor cells to elicit changes in gene expression and metabolism in recipient cells. We have discovered that dietary exosomes from bovine milk can be absorbed by non‐bovine species; studies in murine C2C12 myotube cell cultures suggest that bovine exosomes promote the growth of myofibers.HypothesisThe dietary intake of bovine milk exosomes alters amino acid metabolism, and possibly muscle protein accretion, in non‐bovine species.SignificanceThe dietary intake of exosomes might promote muscle protein accretion in patients with sarcopenia and low‐birth‐weight babies.MethodsC57BL/6 mice, age 3 weeks, were fed an exosome‐depleted (Exo−) AIN93G‐based diet for four weeks; controls were fed an exosome‐sufficient (Exo+) diet. Livers were harvested. The hepatic metabolome was assessed by non‐targeted LC/MS‐MS and by peak intensity analysis; the hepatic transcriptome was assessed by RNAseq using an Illumina HiSeq2500 platform. A second cohort of mice was fed Exo− or Exo+ diets for 4–6 weeks for subsequent analysis of grip strength, respiratory exchange ratio (RER), feeding and activity patterns; skeletal muscle samples are currently analyzed by RNAseq. Statistical significance was assessed using unpaired, two‐tailed t‐test.ResultsHepatic concentrations of several amino acids were significantly higher (up to 18 times) in mice fed the Exo− diet than in Exo+ controls (Fig. 1). The mRNA expression of branched chain amino acid (BCAA) transporters 1 (cytoplasm) and 2 (mitochondria) was greater in mice fed Exo− compared to Exo+ (n.s. for BCAT2; Fig. 2). The RER was not affected by feeding, whereas grip strength was a moderate 5% higher in Exo+ vs. Exo− females after only 4 weeks of feeding (n.s.; not shown). The trend toward a greater grip strength was not caused by differences in food and water consumption or physical activity, which were not significantly different between treatment groups in females.Conclusion & future plansDiets defined by their bovine milk exosome content alter amino acid metabolism in mice. Future studies will investigate protein metabolism by using stable isotopes, and assess muscle protein accretion in response to stimuli such as muscle wasting.Support or Funding InformationNIFA 2015‐67017‐23181, NIFA 2016‐67001‐25301/NIH DK107264, NIH 1P20GM104320, the Gerber Foundation, and USDA Hatch Act and W3002.