Energy restriction upregulates circulating myomiR expression in vivo and in vitro

Abstract

Energy restriction (ER)‐induced weightloss attenuates the rate of protein synthesis, which over time can result inreductions in skeletal muscle mass. Recently, changes in the expression of circulating muscle‐specific microRNA (c‐myomiR)have been suggested to reflect rates of protein synthesis. However, whether an increased expression ofc‐myomiR are associated with lower rates of protein synthesis remains undefined. The present investigation sought to determine whether ER influences c‐myomiR expression, and if changes in c‐myomiR are associated with rates of protein synthesis both in vivo (humans) and in vitro (cultured myocytes). Sixteen older (64 ± 2 yrs) overweight (28.5 ±1.2 kg·m−2) males enrolled in this 35‐day controlled feedingtrial. A 7‐day weight maintenance (WM)period was followed by 28 days of 30% ER; whole‐body protein turnover (15N‐glycine)and c‐myomiR (miR‐1–3p, miR‐133a‐3p, miR‐133b, miR‐206) expression was assessed by RT‐qPCR at the conclusions of WM and ER. Participants lost 4.4 ± 0.3 kg body mass during ER (P < 0.05). Overall, ER upregulated c‐myomiR expression compared to WM (P < 0.05). Expression ofc‐myomiR was inversely associated (r= −0.700, P < 0.05) with whole‐body protein synthesis after ER. Similarly, assessing the expression of c‐myomiR obtained from media that C2C12myotubes were cultured; ER increased c‐myomiR expression by 2.9 ± 0.1 fold and lowered the protein synthesis rate by 2.1 ±0.2 fold compared to control. Corroboration of in vitro and in vivo findings indicates that increased expressions of c‐myomiR maybe noninvasive markers reflective of ER‐induced reductions in the rate protein synthesis.Support or Funding InformationThis material is based on the work supported by the U.S. Department of Agriculture(USDA), under agreement No. 58‐1950‐4‐003 and the US Army Medical Research and Material Command. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the USDA. Mention of trade names or commercial products in this publication is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the USDA. The study was also supported by the Boston Claude D. Pepper Center Older American Independence Centers (OAIC;1P30AG031679). L.M.M is supported by T32NIDDK training grant # 5T32DK062032‐23. D.A.R. is supported by NIA K01 award # KAG047247A‐A1.