Muscle IGF-1-Induced Skeletal Muscle Hypertrophy Evokes Higher Insulin Sensitivity and Carbohydrate Use as Preferential Energy Substrate

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Christoffolete, Marcelo Augusto ; Silva, William Jose ; Ramos, Gracielle Vieira ; Bento, Mirella Ribeiro ; Costa, Monique Oliveira ; Ribeiro, Miriam Oliveira ; Okamoto, Maristela Mitiko ; Lohmann, Tania Helena ; Machado, Ubiratan Fabres ; Musaro, Antonio ; Moriscot, Anselmo Sigari

• Tipo de documento: Artigo Científico
• Fonte: BIOMED RESEARCH INTERNATIONAL; v. 2015, p. 8-pg., 2015-01-01.

Resumo

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 similar 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 similar to 3-fold upregulation in MLC/mIGF-1 animals. We also found a 50% downregulation of PGC1 alpha mRNA levels in MLC/mIGF-1 mouse EDL muscle, suggesting less abundant mitochondria in this tissue. We found no difference in the expression of PPAR alpha and PPAR beta/delta, 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. (AU)

• Processo FAPESP: 06/59862-8 - Plasticidade muscular e homeostase energetica - perfil metabolico e de gasto energetico em animais apresentando aumento de massa muscular induzido por superexpressao de igf-1.
• Beneficiário: Marcelo Augusto Christoffolete
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 12/22488-2 - Expressão de microRNAs em plasticidade muscular esquelética: possíveis inter-relações com o efeito de MuRFs no processo regenerativo
• Beneficiário: William Jose da Silva
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto