MicroRNAs are absorbed in biologically meaningful amounts from nutritionally relevant doses of cow milk and affect gene expression in peripheral blood mononuclear cells, HEK-293 kidney cell cultures, and mouse livers

Scott R. Baier, Christopher Nguyen, Fang Xie, Jennifer R Wood, Janos Zempleni

Research output: Contribution to journalArticle

161 Citations (Scopus)

Abstract

Background: MicroRNAs (miRNAs) regulate genes in animals and plants and can be synthesized endogenously. In milk, miRNAs are encapsulated in exosomes, thereby conferring protection against degradation and facilitating uptake by endocytosis. The majority of bovine miRNAs have nucleotide sequences complementary to human gene transcripts, suggesting that miRNAs in milk might regulate human genes. Objectives: We tested the hypotheses that humans absorb biologically meaningful amounts of miRNAs from nutritionally relevant doses of milk, milk-borne miRNAs regulate human gene expression, and mammals cannot compensate for dietary miRNA depletion by endogenous miRNA synthesis. Methods: Healthy adults (3 men, 2 women; aged 26-49 y) consumed 0.25, 0.5, and 1.0 L of milk in a randomized crossover design. Gene expression studies and milk miRNA depletion studies were conducted in human cell cultures and mice, respectively. For comparison, feeding studies with plant miRNAs from broccoli were conducted in humans. Results: Postprandial concentration time curves suggest that meaningful amounts of miRNA (miR)-29b and miR-200c were absorbed; plasma concentrations of miR-1 did not change (negative control). The expression of runt-related transcription factor 2 (RUNX2), a known target ofmiR-29b, increased by 31%in blood mononuclear cells after milk consumption compared with baseline.When milk exosomeswere added to cell culturemedia,mimicking postprandial concentrations ofmiR-29b and miR-200c, reporter gene activities significantly decreased by 44% and 17%, respectively, compared with vehicle controls in human embryonic kidney 293 cells. When C57BL/6J mice were fed a milk miRNA-depleted diet for 4 wk, plasma miR-29b concentrations were significantly decreased by 61% compared with miRNA-sufficient controls, i.e., endogenous synthesis did not compensate for dietary depletion. Broccoli sprout feeding studies were conducted as a control and elicited no detectable increase in Brassica-specific miRNAs. Conclusion: We conclude that miRNAs in milk are bioactive food compounds that regulate human genes.

Original languageEnglish (US)
Pages (from-to)1495-1500
Number of pages6
JournalJournal of Nutrition
Volume144
Issue number10
DOIs
StatePublished - Jan 1 2014

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HEK293 Cells
MicroRNAs
Blood Cells
Milk
Cell Culture Techniques
Kidney
Gene Expression
Liver
Brassica
Genes
Exosomes

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

@article{aff993a2790c496bb2a37a28cb68ecef,
title = "MicroRNAs are absorbed in biologically meaningful amounts from nutritionally relevant doses of cow milk and affect gene expression in peripheral blood mononuclear cells, HEK-293 kidney cell cultures, and mouse livers",
abstract = "Background: MicroRNAs (miRNAs) regulate genes in animals and plants and can be synthesized endogenously. In milk, miRNAs are encapsulated in exosomes, thereby conferring protection against degradation and facilitating uptake by endocytosis. The majority of bovine miRNAs have nucleotide sequences complementary to human gene transcripts, suggesting that miRNAs in milk might regulate human genes. Objectives: We tested the hypotheses that humans absorb biologically meaningful amounts of miRNAs from nutritionally relevant doses of milk, milk-borne miRNAs regulate human gene expression, and mammals cannot compensate for dietary miRNA depletion by endogenous miRNA synthesis. Methods: Healthy adults (3 men, 2 women; aged 26-49 y) consumed 0.25, 0.5, and 1.0 L of milk in a randomized crossover design. Gene expression studies and milk miRNA depletion studies were conducted in human cell cultures and mice, respectively. For comparison, feeding studies with plant miRNAs from broccoli were conducted in humans. Results: Postprandial concentration time curves suggest that meaningful amounts of miRNA (miR)-29b and miR-200c were absorbed; plasma concentrations of miR-1 did not change (negative control). The expression of runt-related transcription factor 2 (RUNX2), a known target ofmiR-29b, increased by 31{\%}in blood mononuclear cells after milk consumption compared with baseline.When milk exosomeswere added to cell culturemedia,mimicking postprandial concentrations ofmiR-29b and miR-200c, reporter gene activities significantly decreased by 44{\%} and 17{\%}, respectively, compared with vehicle controls in human embryonic kidney 293 cells. When C57BL/6J mice were fed a milk miRNA-depleted diet for 4 wk, plasma miR-29b concentrations were significantly decreased by 61{\%} compared with miRNA-sufficient controls, i.e., endogenous synthesis did not compensate for dietary depletion. Broccoli sprout feeding studies were conducted as a control and elicited no detectable increase in Brassica-specific miRNAs. Conclusion: We conclude that miRNAs in milk are bioactive food compounds that regulate human genes.",
author = "Baier, {Scott R.} and Christopher Nguyen and Fang Xie and Wood, {Jennifer R} and Janos Zempleni",
year = "2014",
month = "1",
day = "1",
doi = "10.3945/jn.114.196436",
language = "English (US)",
volume = "144",
pages = "1495--1500",
journal = "The Journal of nutrition",
issn = "0022-3166",
publisher = "American Society for Nutrition",
number = "10",

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TY - JOUR

T1 - MicroRNAs are absorbed in biologically meaningful amounts from nutritionally relevant doses of cow milk and affect gene expression in peripheral blood mononuclear cells, HEK-293 kidney cell cultures, and mouse livers

AU - Baier, Scott R.

AU - Nguyen, Christopher

AU - Xie, Fang

AU - Wood, Jennifer R

AU - Zempleni, Janos

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Background: MicroRNAs (miRNAs) regulate genes in animals and plants and can be synthesized endogenously. In milk, miRNAs are encapsulated in exosomes, thereby conferring protection against degradation and facilitating uptake by endocytosis. The majority of bovine miRNAs have nucleotide sequences complementary to human gene transcripts, suggesting that miRNAs in milk might regulate human genes. Objectives: We tested the hypotheses that humans absorb biologically meaningful amounts of miRNAs from nutritionally relevant doses of milk, milk-borne miRNAs regulate human gene expression, and mammals cannot compensate for dietary miRNA depletion by endogenous miRNA synthesis. Methods: Healthy adults (3 men, 2 women; aged 26-49 y) consumed 0.25, 0.5, and 1.0 L of milk in a randomized crossover design. Gene expression studies and milk miRNA depletion studies were conducted in human cell cultures and mice, respectively. For comparison, feeding studies with plant miRNAs from broccoli were conducted in humans. Results: Postprandial concentration time curves suggest that meaningful amounts of miRNA (miR)-29b and miR-200c were absorbed; plasma concentrations of miR-1 did not change (negative control). The expression of runt-related transcription factor 2 (RUNX2), a known target ofmiR-29b, increased by 31%in blood mononuclear cells after milk consumption compared with baseline.When milk exosomeswere added to cell culturemedia,mimicking postprandial concentrations ofmiR-29b and miR-200c, reporter gene activities significantly decreased by 44% and 17%, respectively, compared with vehicle controls in human embryonic kidney 293 cells. When C57BL/6J mice were fed a milk miRNA-depleted diet for 4 wk, plasma miR-29b concentrations were significantly decreased by 61% compared with miRNA-sufficient controls, i.e., endogenous synthesis did not compensate for dietary depletion. Broccoli sprout feeding studies were conducted as a control and elicited no detectable increase in Brassica-specific miRNAs. Conclusion: We conclude that miRNAs in milk are bioactive food compounds that regulate human genes.

AB - Background: MicroRNAs (miRNAs) regulate genes in animals and plants and can be synthesized endogenously. In milk, miRNAs are encapsulated in exosomes, thereby conferring protection against degradation and facilitating uptake by endocytosis. The majority of bovine miRNAs have nucleotide sequences complementary to human gene transcripts, suggesting that miRNAs in milk might regulate human genes. Objectives: We tested the hypotheses that humans absorb biologically meaningful amounts of miRNAs from nutritionally relevant doses of milk, milk-borne miRNAs regulate human gene expression, and mammals cannot compensate for dietary miRNA depletion by endogenous miRNA synthesis. Methods: Healthy adults (3 men, 2 women; aged 26-49 y) consumed 0.25, 0.5, and 1.0 L of milk in a randomized crossover design. Gene expression studies and milk miRNA depletion studies were conducted in human cell cultures and mice, respectively. For comparison, feeding studies with plant miRNAs from broccoli were conducted in humans. Results: Postprandial concentration time curves suggest that meaningful amounts of miRNA (miR)-29b and miR-200c were absorbed; plasma concentrations of miR-1 did not change (negative control). The expression of runt-related transcription factor 2 (RUNX2), a known target ofmiR-29b, increased by 31%in blood mononuclear cells after milk consumption compared with baseline.When milk exosomeswere added to cell culturemedia,mimicking postprandial concentrations ofmiR-29b and miR-200c, reporter gene activities significantly decreased by 44% and 17%, respectively, compared with vehicle controls in human embryonic kidney 293 cells. When C57BL/6J mice were fed a milk miRNA-depleted diet for 4 wk, plasma miR-29b concentrations were significantly decreased by 61% compared with miRNA-sufficient controls, i.e., endogenous synthesis did not compensate for dietary depletion. Broccoli sprout feeding studies were conducted as a control and elicited no detectable increase in Brassica-specific miRNAs. Conclusion: We conclude that miRNAs in milk are bioactive food compounds that regulate human genes.

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