@article{555b4cca6f394f16ab267ffff7e7121e,
title = "Concentrations of purine metabolites are elevated in fluids from adults and infants and in livers from mice fed diets depleted of bovine milk exosomes and their RNA cargos",
abstract = "Background: Humans and mice absorb bovine milk exosomes and their RNA cargos. Objectives: The objectives of this study were to determine whether milk exosome- and RNA-depleted (ERD) and exosome- and RNA-sufficient (ERS) diets alter the concentrations of purine metabolites in mouse livers, and to determine whether diets depleted of bovine milk alter the plasma concentration and urine excretion of purine metabolites in adults and infants, respectively. Methods: C57BL/6 mice were fed ERD (providing 2% of the microRNA cargos compared with ERS) and ERS diets starting at age 3 wk; livers were collected at age 7 wk. Plasma and 24-h urine samples were collected from healthy adults who consumed (DCs) or avoided (DAs) dairy products. Spot urine samples were collected from healthy infants fed human milk (HM), milk formula (MF), or soy formula (SF) at age 3 mo. Purine metabolites were analyzed in liver, plasma, and urine; mRNAs and microRNAs were analyzed in the livers of female mice. Results: We found that 9 hepatic purine metabolites in ERD-fed mice were 1.76 ± 0.43 times the concentrations in ERS-fed mice (P < 0.05). Plasma concentrations and urine excretion of purine metabolites in DAs was ≤1.62 ± 0.45 times the concentrations in DCs (P < 0.05). The excretion of 13 purine metabolites in urine from SF infants was ≤175 ± 39 times the excretion in HM and MF infants (P < 0.05). mRNA expression of 5-nucleotidase, cytosolic IIIB, and adenosine deaminase in mice fed ERD was 0.64 ± 0.52 and 0.60 ± 0.28 times the expression in mice fed ERS, respectively. Conclusion: Diets depleted of bovine-milk exosomes and RNA cargos caused increases in hepatic purine metabolites in mice, and in plasma and urine from human adults and infants, compared with exosome-sufficient controls. These findings are important, because purines play a role in intermediary metabolism and cell signaling.",
keywords = "Bovine milk, Exosomes, Metabolomics, Purines, RNA",
author = "Ana Aguilar-Lozano and Scott Baier and Ryan Grove and Jiang Shu and David Giraud and Amy Leiferman and Mercer, {Kelly E.} and Juan Cui and Badger, {Thomas M.} and Jiri Adamec and Aline Andres and Janos Zempleni",
note = "Funding Information: This material is based upon work that is supported by the National Institute of Food and Agriculture (NIFA), USDA, under award numbers 2015-67017-23181 and 2016-67001-25301, NIH grant 1P20GM104320, Egg Nutrition Center, the Gerber Foundation, the University of Nebraska Agricultural Research Division (Hatch Act), and USDA multistate group W3002 (all to JZ), and a Food for Health grant from the University of Nebraska President's Office (to JC and JZ). Funding for the clinical study was from the USDA-Agricultural Research Service Project 6026-51000-010-05S (to AA and TB). JZ serves as a consultant for PureTech Health, Inc. The granting agencies had no influence on the study design; the collection, analysis, and interpretation of the data; the writing of the manuscript; or the decision to submit the manuscript for publication. Funding Information: This material is based upon work that is supported by the National Institute of Food and Agriculture (NIFA), USDA, under award numbers 2015-67017-23181 and 2016-67001-25301, NIH grant 1P20GM104320, Egg Nutrition Center, the Gerber Foundation, the University of Nebraska Agricultural Research Division (Hatch Act), and USDA multistate group W3002 (all to JZ), and a Food for Health grant from the University of Nebraska President{\textquoteright}s Office (to JC and JZ). Funding for the clinical study was from the USDA-Agricultural Research Service Project 6026-51000-010-05S (to AA and TB). JZ serves as a consultant for PureTech Health, Inc. The granting agencies had no influence on the study design; the collection, analysis, and interpretation of the data; the writing of the manuscript; or the decision to submit the manuscript for publication. Supplemental Tables 1–5 and Supplemental Figures 1–4 are available from the “Supplementary data” link in the online posting of the article and from the same link in the online table of contents at https://academic.oup.com/jn/. Author disclosures: AA-L, SB, RG, JS, DG, AL, JA, JC, KEM, TMB, AA, and JZ, no conflicts of interest. Address correspondence to JZ (e-mail: jzempleni2@unl.edu). Abbreviations used: Ct, cycle threshold; DA, dairy avoider; DC, dairy consumer; ERD, exosome– and RNA-depleted; ERS, exosome-and RNA-sufficient; HILIC-MRM-MS/MS, hydrophilic-interaction chromatography-multiple reaction monitoring-tandem mass spectrometry; HM, human milk; MF, milk formula; RNA-Seq, RNA-sequencing; SF, soy formula. Publisher Copyright: {\textcopyright} 2018 American Society for Nutrition. All rights reserved.",
year = "2018",
month = dec,
day = "1",
doi = "10.1093/jn/nxy223",
language = "English (US)",
volume = "148",
pages = "1886--1894",
journal = "Journal of Nutrition",
issn = "0022-3166",
publisher = "American Society for Nutrition",
number = "12",
}