Cluster analysis tests the importance of myogenic gene expression during myofiber hypertrophy in humans

• Published in: Journal of applied physiology (1985) Vol. 102; no. 6; pp. 2232 - 2239
• Main Authors: Bamman, Marcas M, Petrella, John K, Kim, Jeong-su, Mayhew, David L, Cross, James M
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Physiological Soc 01.06.2007; American Physiological Society
• Subjects: Adult; Aged; Biological and medical sciences; Biomarkers - metabolism; Cluster Analysis; Female; Fundamental and applied biological sciences. Psychology; Gene Expression; Gene Expression Profiling - methods; Gene Expression Regulation; Humans; Hypertrophy - metabolism; Hypertrophy - pathology; Insulin; Male; Middle Aged; Muscle Contraction - physiology; Muscle Proteins - metabolism; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Muscular system; Physical Exertion - physiology; Physical training; Protein synthesis; Proteins; Human; insulin-like growth factor I; Growth; myogenin; muscle fiber; Muscular fiber; Gene expression; Insulin like growth factor 1; Striated muscle; muscle growth; Vertebrata; Mammalia; Hypertrophy
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.00024.2007

Departments of 1 Physiology and Biophysics and of 3 Surgery, and 4 Medical Scientist Training Program, The University of Alabama at Birmingham; and 2 Geriatric Research, Education, and Clinical Center, Birmingham Veterans Affairs Medical Center, Birmingham, Alabama Submitted 6 January 2007 ; accepted in final form 19 March 2007 We applied K-means cluster analysis to test the hypothesis that muscle-specific factors known to modulate protein synthesis and satellite cell activity would be differentially expressed during progressive resistance training (PRT, 16 wk) in 66 human subjects experiencing extreme, modest, and failed myofiber hypertrophy. Muscle mRNA expression of IGF-I isoform Ea (IGF-IEa), mechanogrowth factor (MGF, IGF-IEc), myogenin, and MyoD were assessed in muscle biopsies collected at baseline (T1) and 24 h after the first (T2) and last (T3) loading bouts from previously untrained subjects clustered as extreme responders (Xtr, n = 17), modest responders (Mod, n = 32), and nonresponders (Non, n = 17) based on mean myofiber hypertrophy. Myofiber growth averaged 2,475 µm 2 in Xtr, 1,111 µm 2 in Mod, and –16 µm 2 in Non. Main training effects revealed increases in all transcripts (46–83%, P < 0.005). For the entire cohort, IGF-IEa, MGF, and myogenin mRNAs were upregulated by T2 ( P < 0.05), while MyoD did not increase significantly until T3 ( P < 0.001). Within clusters, MGF and myogenin upregulation was robust in Xtr (126% and 65%) and Mod (73% and 41%) vs. no changes in Non. While significant in all clusters by T3, IGF-IEa increased most in Xtr (105%) and least in Non (44%). Although MyoD expression increased overall, no changes within clusters were detected. We reveal for the first time that MGF and myogenin transcripts are differentially expressed in subjects experiencing varying degrees of PRT-mediated myofiber hypertrophy. The data strongly suggest the load-mediated induction of these genes may initiate important actions necessary to promote myofiber growth during PRT, while the role of MyoD is less clear. muscle growth; myogenin; insulin-like growth factor I; muscle fiber Address for reprint requests and other correspondence: M. M. Bamman, UAB Dept. of Physiology and Biophysics, Core Muscle Research Laboratory, GRECC/11G, Veterans Affairs Medical Center, 1530 3rd Ave. South, Birmingham, AL 35294-0001 (e-mail: mbamman{at}uab.edu )