Skeletal Muscle miR133a Expression in Short‐Term Voluntary Wheel Exercise and High‐Fat Diet in Rats

Abstract

Micro RNAs (miR) are small non‐coding RNA that regulate gene expression at the post‐transcriptional level. miR133a is abundant in cardiac and skeletal muscle. miR133a is known to oppose the fibrotic process upregulated in ischemic or diabetic heart disease (Chen et al., 2014). Recently, knockdown of miR133a in transgenic mice resulted in blunted skeletal muscle mitochondrial biogenesis and function in response to exercise training [Nie et al. (2016)] suggesting a major role for miR133a in regulating the normal skeletal muscle adaptive response to exercise. Among other miR, miR133a is reported as downregulated in type 2 diabetes mellitus (T2DM). As miR133a may regulate cell signaling pathways that promote insulin signaling and mitochondrial biogenesis and function, modulation of miR133a expression could contribute to the effect of regular, moderate exercise to ameliorate the metabolic dysfunction associated with T2DM and/or high fat nutrient stress. The working hypothesis for this pilot study is that miR133a is upregulated early in the adoption of regular exercise. We compared the expression of miR133a in sedentary Harlan Sprague Dawley rats and rats allowed to exercise voluntarily on cage wheels, who were fed normal rat chow or a high fat diet (TestDiet 58Y1 Blue; 60% energy from fat) for 10 days (N=4 per group). Wheels were removed from the cages approximately 12 hrs prior to euthanization. Total mRNA was extracted from gastrocnemius muscle. miR reverse transcription and real time PCR were performed using Applied Biosystems Taqman Universal Master Mix II Protocol without UNG. Relative gene expression of miR133a was determined with the 2^(‐ΔΔCt) method with normalization to miR191. miR133a was expressed as fold‐change from the mean of the sedentary‐normal chow group. Daily exercise distance (m) increased progressively over the 10‐day period, ranging from 1307–4683 m/day. There was no difference (p=0.6) in the exercise pattern between the rats fed normal or high fat diet. Short term, voluntary wheel exercise did not cause a significant change in expression of miR133a in the gastrocnemius of exercised or sedentary rats on either normal or high fat diet (p=0.6). Interestingly, linear regression of mi133a fold‐change versus total distance run over the 10 days in the 8 wheel‐running rats revealed a mild correlation (R2=0.5, P=0.04), indicating that higher exercise volumes were associated with greater expression of miR133a. This preliminary data indicated variability in the relative expression of intracellular miR133a in gastrocnemius muscle in voluntarily exercising rats could be related to the volume of daily exercise.Support or Funding InformationThis study was supported by Midwestern University and APS 2018 Frontiers in Physiology Research Community Leaders Professional Development Fellowship to Sowmya Anjur.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.