TY - JOUR
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 -