PMID- 30548426 OWN - NLM STAT- MEDLINE DCOM- 20190917 LR - 20231004 IS - 2051-817X (Electronic) IS - 2051-817X (Linking) VI - 6 IP - 23 DP - 2018 Dec TI - PI3K-AKT-FOXO1 pathway targeted by skeletal muscle microRNA to suppress proteolytic gene expression in response to carbohydrate intake during aerobic exercise. PG - e13931 LID - 10.14814/phy2.13931 [doi] LID - e13931 AB - Ingesting protein and carbohydrate together during aerobic exercise suppresses the expression of specific skeletal muscle microRNA and promotes muscle hypertrophy. Determining whether there are independent effects of carbohydrate and protein on microRNA will allow for a clearer understanding of the mechanistic role microRNA serve in regulating skeletal muscle protein synthetic and proteolytic responses to nutrition and exercise. This study determined skeletal muscle microRNA responses to aerobic exercise with or without carbohydrate, and recovery whey protein (WP). Seventeen males were randomized to consume carbohydrate (CHO; 145 g; n = 9) or non-nutritive control (CON; n = 8) beverages during exercise. Muscle was collected before (BASE) and after 80 min of steady-state exercise (1.7 +/- 0.3 V̇O(2) L.min(-1) ) followed by a 2-mile time trial (17.9 +/- 3.5 min; POST), and 3-h into recovery after consuming WP (25 g; REC). RT-qPCR was used to determine microRNA and mRNA expression. Bioinformatics analysis was conducted using the mirPath software. Western blotting was used to assess protein signaling. The expression of six microRNA (miR-19b-3p, miR-99a-5p, miR-100-5p, miR-222-3p, miR-324-3p, and miR-486-5p) were higher (P < 0.05) in CHO compared to CON, all of which target the PI3K-AKT, ubiquitin proteasome, FOXO, and mTORC1 pathways. p-AKT(T)(hr473) and p-FOXO1(Thr24) were higher (P < 0.05) in POST CHO compared to CON. The expression of PTEN was lower (P < 0.05) in REC CHO than CON, while MURF1 was lower (P < 0.05) POST CHO than CON. These findings suggest the mechanism by which microRNA facilitate skeletal muscle adaptations in response to exercise with carbohydrate and protein feeding is by inhibiting markers of proteolysis. CI - (c) 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society. FAU - Margolis, Lee M AU - Margolis LM AD - Military Nutrition Division, U.S. Army Research Institute of Environmental Medicine, Natick, Massachusetts. AD - Oak Ridge Institute of Science and Education, Oak Ridge, Tennessee. FAU - Berryman, Claire E AU - Berryman CE AD - Military Nutrition Division, U.S. Army Research Institute of Environmental Medicine, Natick, Massachusetts. AD - Oak Ridge Institute of Science and Education, Oak Ridge, Tennessee. AD - Department of Nutrition, Food, and Exercise Sciences, Florida State University, Tallahassee, Florida. FAU - Murphy, Nancy E AU - Murphy NE AD - Military Nutrition Division, U.S. Army Research Institute of Environmental Medicine, Natick, Massachusetts. FAU - Carrigan, Christopher T AU - Carrigan CT AD - Military Nutrition Division, U.S. Army Research Institute of Environmental Medicine, Natick, Massachusetts. FAU - Young, Andrew J AU - Young AJ AD - Military Nutrition Division, U.S. Army Research Institute of Environmental Medicine, Natick, Massachusetts. AD - Oak Ridge Institute of Science and Education, Oak Ridge, Tennessee. FAU - Carbone, John W AU - Carbone JW AD - Oak Ridge Institute of Science and Education, Oak Ridge, Tennessee. AD - School of Health Sciences, Eastern Michigan University, Ypsilanti, Michigan. FAU - Pasiakos, Stefan M AU - Pasiakos SM AD - Military Nutrition Division, U.S. Army Research Institute of Environmental Medicine, Natick, Massachusetts. LA - eng PT - Journal Article PT - Randomized Controlled Trial PL - United States TA - Physiol Rep JT - Physiological reports JID - 101607800 RN - 0 (Dietary Carbohydrates) RN - 0 (Dietary Proteins) RN - 0 (FOXO1 protein, human) RN - 0 (Forkhead Box Protein O1) RN - 0 (MicroRNAs) RN - 0 (Muscle Proteins) RN - 0 (Tripartite Motif Proteins) RN - EC 2.3.2.27 (TRIM63 protein, human) RN - EC 2.3.2.27 (Ubiquitin-Protein Ligases) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 3.1.3.67 (PTEN Phosphohydrolase) RN - EC 3.1.3.67 (PTEN protein, human) SB - IM MH - Dietary Carbohydrates/administration & dosage/*pharmacology MH - Dietary Proteins/administration & dosage/pharmacology MH - Forkhead Box Protein O1/genetics/metabolism MH - Humans MH - Male MH - MicroRNAs/genetics/*metabolism MH - Muscle Proteins/genetics/metabolism MH - Muscle, Skeletal/drug effects/*metabolism/physiology MH - PTEN Phosphohydrolase/genetics/metabolism MH - Phosphatidylinositol 3-Kinases/genetics/metabolism MH - Physical Conditioning, Human/*methods MH - *Proteolysis MH - Proto-Oncogene Proteins c-akt/genetics/metabolism MH - *Signal Transduction MH - Tripartite Motif Proteins/genetics/metabolism MH - Ubiquitin-Protein Ligases/genetics/metabolism MH - Young Adult PMC - PMC6289907 OTO - NOTNLM OT - miR-206 OT - miR-486 OT - muscle protein breakdown OT - muscle protein synthesis OT - myomiR OT - whey protein EDAT- 2018/12/15 06:00 MHDA- 2019/09/19 06:00 PMCR- 2018/12/11 CRDT- 2018/12/15 06:00 PHST- 2018/11/05 00:00 [received] PHST- 2018/11/06 00:00 [revised] PHST- 2018/12/15 06:00 [entrez] PHST- 2018/12/15 06:00 [pubmed] PHST- 2019/09/19 06:00 [medline] PHST- 2018/12/11 00:00 [pmc-release] AID - PHY213931 [pii] AID - 10.14814/phy2.13931 [doi] PST - ppublish SO - Physiol Rep. 2018 Dec;6(23):e13931. doi: 10.14814/phy2.13931.