Comprehensive profiling of the circulatory miRNAome response to a high protein diet in elderly men: A potential role in inflammatory response modulation

Farha Ramzan; Cameron J Mitchell; Amber M Milan; William Schierding; Nina Zeng; Pankaja Sharma; Sarah M Mitchell; Randall F D'Souza; Scott O Knowles; Nicole C Roy; Anders Mikael Sjödin; Karl-Heinz Wagner; David Cameron-Smith

doi:10.1002/mnfr.201800811

Comprehensive profiling of the circulatory miRNAome response to a high protein diet in elderly men: A potential role in inflammatory response modulation

Farha Ramzan, Cameron J Mitchell, Amber M Milan, William Schierding, Nina Zeng, Pankaja Sharma, Sarah M Mitchell, Randall F D'Souza, Scott O Knowles, Nicole C Roy, Anders Mikael Sjödin, Karl-Heinz Wagner, David Cameron-Smith^*

^*Corresponding author for this work

Obesity Research

6 Citations (Scopus)

Abstract

Scope: MicroRNA are critical to the coordinated post-transcriptional regulation of gene expression, yet few studies have addressed the influence of habitual diet on microRNA expression. High protein diets impact cardiometabolic health and body composition in the elderly suggesting the possibility of a complex systems response. Therefore, high-throughput small RNA sequencing technology is applied in response to doubling the protein recommended dietary allowance (RDA) over 10 weeks in older men to examine alterations in circulating miRNAome.

Methods and Results: Older men (n = 31; 74.1 ± 0.6 y) are randomized to consume either RDA (0.8 g kg ⁻¹ day ⁻¹ ) or 2RDA (1.6 g kg ⁻¹ day ⁻¹ ) of protein for 10 weeks. Downregulation of five microRNAs (miR-125b-5p, -100-5p, -99a-5p, -23b-3p, and -203a) is observed following 2RDA with no changes in the RDA. In silico functional analysis highlights target gene enrichment in inflammation-related pathways. qPCR quantification of predicted inflammatory genes (TNFα, IL-8, IL-6, pTEN, PPP1CB, and HOXA1) in peripheral blood mononuclear cells shows increased expression following 2RDA diet (p ≤ 0.05).

Conclusion: The study findings suggest a possible selective alteration in the post-transcriptional regulation of the immune system following a high protein diet. However, very few microRNAs are altered despite a large change in the dietary protein.

Original language	English
Article number	1800811
Journal	Molecular Nutrition & Food Research
Volume	63
Issue number	8
Number of pages	10
ISSN	1613-4125
DOIs	https://doi.org/10.1002/mnfr.201800811
Publication status	Published - Apr 2019

Keywords

Gene expression
Inflammation
microRNA
Peripheral blood mononuclear cells
Sequencing

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10.1002/mnfr.201800811

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Ramzan, F., Mitchell, C. J., Milan, A. M., Schierding, W., Zeng, N., Sharma, P., Mitchell, S. M., D'Souza, R. F., Knowles, S. O., Roy, N. C., Sjödin, A. M., Wagner, K-H., & Cameron-Smith, D. (2019). Comprehensive profiling of the circulatory miRNAome response to a high protein diet in elderly men: A potential role in inflammatory response modulation. Molecular Nutrition & Food Research, 63(8), [1800811]. https://doi.org/10.1002/mnfr.201800811

Comprehensive profiling of the circulatory miRNAome response to a high protein diet in elderly men : A potential role in inflammatory response modulation. / Ramzan, Farha; Mitchell, Cameron J; Milan, Amber M et al.

In: Molecular Nutrition & Food Research, Vol. 63, No. 8, 1800811, 04.2019.

Research output: Contribution to journal › Journal article › Research › peer-review

Ramzan, F, Mitchell, CJ, Milan, AM, Schierding, W, Zeng, N, Sharma, P, Mitchell, SM, D'Souza, RF, Knowles, SO, Roy, NC, Sjödin, AM, Wagner, K-H & Cameron-Smith, D 2019, 'Comprehensive profiling of the circulatory miRNAome response to a high protein diet in elderly men: A potential role in inflammatory response modulation', Molecular Nutrition & Food Research, vol. 63, no. 8, 1800811. https://doi.org/10.1002/mnfr.201800811

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title = "Comprehensive profiling of the circulatory miRNAome response to a high protein diet in elderly men: A potential role in inflammatory response modulation",

abstract = " Scope: MicroRNA are critical to the coordinated post-transcriptional regulation of gene expression, yet few studies have addressed the influence of habitual diet on microRNA expression. High protein diets impact cardiometabolic health and body composition in the elderly suggesting the possibility of a complex systems response. Therefore, high-throughput small RNA sequencing technology is applied in response to doubling the protein recommended dietary allowance (RDA) over 10 weeks in older men to examine alterations in circulating miRNAome. Methods and Results: Older men (n = 31; 74.1 ± 0.6 y) are randomized to consume either RDA (0.8 g kg −1 day −1 ) or 2RDA (1.6 g kg −1 day −1 ) of protein for 10 weeks. Downregulation of five microRNAs (miR-125b-5p, -100-5p, -99a-5p, -23b-3p, and -203a) is observed following 2RDA with no changes in the RDA. In silico functional analysis highlights target gene enrichment in inflammation-related pathways. qPCR quantification of predicted inflammatory genes (TNFα, IL-8, IL-6, pTEN, PPP1CB, and HOXA1) in peripheral blood mononuclear cells shows increased expression following 2RDA diet (p ≤ 0.05). Conclusion: The study findings suggest a possible selective alteration in the post-transcriptional regulation of the immune system following a high protein diet. However, very few microRNAs are altered despite a large change in the dietary protein. ",

keywords = "Gene expression, Inflammation, microRNA, Peripheral blood mononuclear cells, Sequencing",

author = "Farha Ramzan and Mitchell, {Cameron J} and Milan, {Amber M} and William Schierding and Nina Zeng and Pankaja Sharma and Mitchell, {Sarah M} and D'Souza, {Randall F} and Knowles, {Scott O} and Roy, {Nicole C} and Sj{\"o}din, {Anders Mikael} and Karl-Heinz Wagner and David Cameron-Smith",

note = "CURIS 2019 NEXS 144",

year = "2019",

month = apr,

doi = "10.1002/mnfr.201800811",

language = "English",

volume = "63",

journal = "Molecular Nutrition & Food Research",

issn = "1613-4125",

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T1 - Comprehensive profiling of the circulatory miRNAome response to a high protein diet in elderly men

T2 - A potential role in inflammatory response modulation

AU - Ramzan, Farha

AU - Mitchell, Cameron J

AU - Milan, Amber M

AU - Schierding, William

AU - Zeng, Nina

AU - Sharma, Pankaja

AU - Mitchell, Sarah M

AU - D'Souza, Randall F

AU - Knowles, Scott O

AU - Roy, Nicole C

AU - Sjödin, Anders Mikael

AU - Wagner, Karl-Heinz

AU - Cameron-Smith, David

N1 - CURIS 2019 NEXS 144

PY - 2019/4

Y1 - 2019/4

N2 - Scope: MicroRNA are critical to the coordinated post-transcriptional regulation of gene expression, yet few studies have addressed the influence of habitual diet on microRNA expression. High protein diets impact cardiometabolic health and body composition in the elderly suggesting the possibility of a complex systems response. Therefore, high-throughput small RNA sequencing technology is applied in response to doubling the protein recommended dietary allowance (RDA) over 10 weeks in older men to examine alterations in circulating miRNAome. Methods and Results: Older men (n = 31; 74.1 ± 0.6 y) are randomized to consume either RDA (0.8 g kg −1 day −1 ) or 2RDA (1.6 g kg −1 day −1 ) of protein for 10 weeks. Downregulation of five microRNAs (miR-125b-5p, -100-5p, -99a-5p, -23b-3p, and -203a) is observed following 2RDA with no changes in the RDA. In silico functional analysis highlights target gene enrichment in inflammation-related pathways. qPCR quantification of predicted inflammatory genes (TNFα, IL-8, IL-6, pTEN, PPP1CB, and HOXA1) in peripheral blood mononuclear cells shows increased expression following 2RDA diet (p ≤ 0.05). Conclusion: The study findings suggest a possible selective alteration in the post-transcriptional regulation of the immune system following a high protein diet. However, very few microRNAs are altered despite a large change in the dietary protein.

AB - Scope: MicroRNA are critical to the coordinated post-transcriptional regulation of gene expression, yet few studies have addressed the influence of habitual diet on microRNA expression. High protein diets impact cardiometabolic health and body composition in the elderly suggesting the possibility of a complex systems response. Therefore, high-throughput small RNA sequencing technology is applied in response to doubling the protein recommended dietary allowance (RDA) over 10 weeks in older men to examine alterations in circulating miRNAome. Methods and Results: Older men (n = 31; 74.1 ± 0.6 y) are randomized to consume either RDA (0.8 g kg −1 day −1 ) or 2RDA (1.6 g kg −1 day −1 ) of protein for 10 weeks. Downregulation of five microRNAs (miR-125b-5p, -100-5p, -99a-5p, -23b-3p, and -203a) is observed following 2RDA with no changes in the RDA. In silico functional analysis highlights target gene enrichment in inflammation-related pathways. qPCR quantification of predicted inflammatory genes (TNFα, IL-8, IL-6, pTEN, PPP1CB, and HOXA1) in peripheral blood mononuclear cells shows increased expression following 2RDA diet (p ≤ 0.05). Conclusion: The study findings suggest a possible selective alteration in the post-transcriptional regulation of the immune system following a high protein diet. However, very few microRNAs are altered despite a large change in the dietary protein.

KW - Gene expression

KW - Inflammation

KW - microRNA

KW - Peripheral blood mononuclear cells

KW - Sequencing

U2 - 10.1002/mnfr.201800811

DO - 10.1002/mnfr.201800811

M3 - Journal article

C2 - 30892810

AN - SCOPUS:85063686824

SN - 1613-4125

VL - 63

JO - Molecular Nutrition & Food Research

JF - Molecular Nutrition & Food Research

IS - 8

M1 - 1800811

ER -

Comprehensive profiling of the circulatory miRNAome response to a high protein diet in elderly men: A potential role in inflammatory response modulation

Abstract

Keywords

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