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. In skeletal muscle, miR133a is best known for its regulatory role in myogenesis and differentiation. Nie (2016) found that muscle miR133a expression increased after acute exercise and with 12w of treadmill exercise training in mice. Knockdown of miR133a in transgenic mice resulted in blunted skeletal muscle mitochondrial biogenesis and function in response to exercise training (Nie, 2016) suggesting a role for miR133a in regulating the normal skeletal muscle metabolic adaptive response to exercise. Among other miR, skeletal muscle miR133a is reported as downregulated in insulin-resistant muscle. Insulin resistance in mice fed a high-fat diet is detectable after 3 days on diet (Lee, 2011). In this study, voluntary, rather than forced, exercise was employed to test whether miR133a expression is regulated early in the adoption of increased daily physical activity.