title: Essential amino acids increase microRNA-499, -208b, and -23a and downregulate myostatin and myocyte enhancer factor 2C mRNA expression in human skeletal muscle.
abstract: 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.
authors.affiliation: Department of Physical Therapy, Division of Rehabilitation Science, University of Texas Medical Branch, Galveston, TX 77555, USA. mjdrummo@utmb.edu
authors.forename: Micah J
authors.initials: MJ
authors.lastname: Drummond
authors.forename: Erin L
authors.initials: EL
authors.lastname: Glynn
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Fry
authors.forename: Shaheen
authors.initials: S
authors.lastname: Dhanani
authors.forename: Elena
authors.initials: E
authors.lastname: Volpi
authors.forename: Blake B
authors.initials: BB
authors.lastname: Rasmussen
mesh_terms: D000328:Adult; D000596:Amino Acids / Q000097:blood; D000601:Amino Acids, Essential / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D017931:DNA Primers; D018076:DNA, Complementary / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D026161:MADS Domain Proteins / Q000235:genetics*; D064326:MEF2 Transcription Factors; D008297:Male; D035683:MicroRNAs / Q000187:drug effects / Q000235:genetics*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology*; D018006:Myogenic Regulatory Factors / Q000235:genetics*; D055435:Myostatin / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics*
chemical_list: D000596:Amino Acids; D000601:Amino Acids, Essential; D001786:Blood Glucose; D017931:DNA Primers; D018076:DNA, Complementary; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; C578040:MEF2C protein, human; D035683:MicroRNAs; D018006:Myogenic Regulatory Factors; D055435:Myostatin; D012333:RNA, Messenger