Muscle IGF-1-induced skeletal muscle hypertrophy evokes higher insulin sensitivity and carbohydrate use as preferential energy substrate.
We characterized the metabolic profile of transgenic mice exhibiting enhanced muscle mass driven by increased mIGF-1 expression (MLC/mIGF-1). As expected, 6-month-old MLC/mIGF-1 mice were heavier than age-matched wild type (WT) mice (37.4 ± 0.3 versus 31.8 ± 0.6 g, resp.). MLC/mIGF-1 mice had higher respiratory quotient when compared to WT (0.9 ± 0.03 versus 0.74 ± 0.02, resp.) suggesting a preference for carbohydrate as the major fuel source. MLC/mIGF-1 mice had a higher rate of glucose disposal when compared to WT (3.25 ± 0.14 versus 2.39 ± 0.03%/min, resp.). The higher disposal rate correlated to ∼ 2-fold higher GLUT4 content in the extensor digitorum longus (EDL) muscle. Analysis of mRNA content for the glycolysis-related gene PFK-1 showed ∼ 3-fold upregulation in MLC/mIGF-1 animals. We also found a 50% downregulation of PGC1α mRNA levels in MLC/mIGF-1 mouse EDL muscle, suggesting less abundant mitochondria in this tissue. We found no difference in the expression of PPARα and PPARβ/δ, suggesting no modulation of key elements in oxidative metabolism. These data together suggest a shift in metabolism towards higher carbohydrate utilization, and that could explain the increased insulin sensitivity of hypertrophied skeletal muscle in MLC/mIGF-1 mice.
Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, SP, Brazil ; Centro de Ciências Naturais e Humanas (CCNH), Universidade Federal do ABC (UFABC), 09210-580 Santo André, SP, Brazil.
Marcelo Augusto
MA
Christoffolete
Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, SP, Brazil.
William Jose
0000-0001-6969-3464
WJ
Silva
Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, SP, Brazil.
Gracielle Vieira
GV
Ramos
Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, SP, Brazil.
Mirella Ribeiro
MR
Bento
Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, SP, Brazil.
Monique Oliveira
MO
Costa
Biological and Health Science Center, Mackenzie Presbyterian University, 01302-907 São Paulo, SP, Brazil.
Miriam Oliveira
MO
Ribeiro
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, SP, Brazil.
Maristela Mitiko
MM
Okamoto
Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, SP, Brazil.
Tania Helena
TH
Lohmann
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, SP, Brazil.
Ubiratan Fabres
UF
Machado
Institute Pasteur Cenci Bolognetti, DAHFMO, Unit of Histology and Medical Embryology, IIM, Sapienza University of Rome, 00161 Rome, Italy.
Antonio
A
Musarò
Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, SP, Brazil.
Anselmo Sigari
AS
Moriscot
D000818:Animals; D050260:Carbohydrate Metabolism / Q000502:physiology*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006984:Hypertrophy / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D051275:Glucose Transporter Type 4; D007328:Insulin; D009124:Muscle Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D047492:Peroxisome Proliferator-Activated Receptors; C485290:Ppargc1a protein, mouse; D012333:RNA, Messenger; C495694:Slc2a4 protein, rat; D014157:Transcription Factors; C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I