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Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions

Essential Amino Acids Increase MicroRNA-499, -208b, and -23a and Downregulate Myostatin and Myocyte Enhancer Factor 2C mRNA Expression in Human Skeletal Muscle^1,2

³ Departments of Physical Therapy, University of Texas Medical Branch, Galveston, TX 77555 ⁴ Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555 ⁵ Divisions of Rehabilitation Science, University of Texas Medical Branch, Galveston, TX 77555 ⁶ Geriatrics, University of Texas Medical Branch, Galveston, TX 77555 ⁷ Sealy Center on Aging, University of Texas Medical Branch, Galveston, TX 77555

Essential amino acids (EAA) stimulate muscle protein synthesis in humans. However, little is known about whether microRNAs (miRNA) and genes associated with muscle growth are expressed differently following EAA ingestion. Our purpose in this experiment was to determine whether miRNA and growth-related mRNA expressed in skeletal muscle are up- or downregulated in humans following the ingestion of EAA. We hypothesized that EAA would alter miRNA expression in skeletal muscle as well as select growth-related genes. Muscle biopsies were obtained from the vastus lateralis of 7 young adult participants (3 male, 4 female) before and 3 h after ingesting 10 g of EAA. Muscle samples were analyzed for muscle miRNA (miR-499, -208b, -23a, -1, -133a, and -206) and muscle-growth related genes [MyoD1, myogenin, myostatin, myocyte enhancer factor C (MEF2C), follistatin-like-1 (FSTL1), histone deacytylase 4, and serum response factor mRNA] before and after EAA ingestion using real-time PCR. Following EAA ingestion, miR-499, -208b, -23a, -1, and pri-miR-206 expression increased (P < 0.05). The muscle-growth genes MyoD1 and FSTL1 mRNA expression increased (P < 0.05), and myostatin and MEF2C mRNA were downregulated following EAA ingestion (P < 0.05). We conclude that miRNA and growth-related genes expressed in skeletal muscle are rapidly altered within hours following EAA ingestion. Further work is needed to determine whether these miRNA are post-transcriptional regulators of growth-related genes following an anabolic stimulus.

^* To whom correspondence should be addressed. E-mail: mjdrummo{at}utmb.edu.

Manuscript received 10 July 2009. Initial review completed 28 August 2009. Revision accepted 7 October 2009.