Upregulation of circulating myomiR following short-term energy restriction is inversely associated with whole body protein synthesis

Authors: MARGOLIS, LEE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; RIVAS, DONATO - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; PASIAKOS, STEFAN - Us Army Research; MCCLUNG, JAMES - Us Army Research; CEGLIA, LISA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; FIELDING, ROGER - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: American Journal of Physiology - Regulatory Integrative & Comparative Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/26/2017
Publication Date: 9/11/2017
Citation: Margolis, L., Rivas, D.A., Pasiakos, S., McClung, J.P., Ceglia, L., Fielding, R.A. 2017. Upregulation of circulating myomiR following short-term energy restriction is inversely associated with whole body protein synthesis. American Journal of Physiology - Regulatory Integrative & Comparative Physiology. 313(3):R298-R304. https://doi.org/10.1152/ajpregu.00054.2017.

Interpretive Summary: MicroRNA (miR) are small non-coding RNA that play a role in regulating the expression of many genes in many cell types, including skeletal muscle. In this preliminary study, we examined several micro RNAs known to affect skeletal muscle gene expression in the serum of older men who underwent a short term (28 day) low calorie diet (ER) preceded by 7 days of weight maintenance (WM). Participants lost 4.4 +/- 0.3 kg body weight during ER (P < 0.05). Following 28 days of ER miR-133a and miR-133b expression were upregulated (P < 0.05) compared to WM. We observed associations between miR levels and whole-body protein synthesis (r = -0.729; P < 0.05). Findings from the present investigation provide evidence that upregulation in miR in response to short-term ER are associated with lower rates of whole-body protein synthesis.

Technical Abstract: The objective of the present investigation was to determine whether energy restriction (ER) influences expression of skeletal muscle-specific microRNA (miRNA) in circulation (c-myomiR) and whether changes in c-myomiR are associated with rates of whole body protein synthesis. Sixteen older (64 +/- 2 yr) overweight (28.5 +/- 1.2 kg/m^2) men enrolled in this 35-day controlled feeding trial. A 7-day weight maintenance (WM) period was followed by 28 days of 30% ER. Whole body protein turnover was determined from [15N]glycine enrichments in 24-h urine collections, and c-myomiR (miR-1-3p, miR-133a-3p, miR-133b, and miR-206) expression was assessed from serum samples by RT-quantitative PCR upon completion of the WM and ER periods. Participants lost 4.4 +/- 0.3 kg body mass during ER (P < 0.05). After 28 days of ER, miR-133a and miR-133b expression was upregulated (P < 0.05) compared with WM. When all four c-myomiR were grouped as c-myomiR score (sum of the median fold change of all myomiR), overall expression of c-myomiR was higher (P < 0.05) at ER than WM. Backward linear regression analysis of whole body protein synthesis and breakdown and carbohydrate, fat, and protein oxidation determined protein synthesis to be the strongest predictor of c-myomiR score. An inverse association (P < 0.05) was observed with ER c-myomiR score and whole body protein synthesis (r= -0.729, r^2= -0.530). Findings from the present investigation provide evidence that upregulation of c-myomiR expression profiles in response to short-term ER is associated with lower rates of whole body protein synthesis.