Muscle IGF-1-induced skeletal muscle hypertrophy evokes higher insulin sensitivity and carbohydrate use as preferential energy substrate

Christoffolete M.A.; Silva W.J.; Ramos G.V.; Bento M.R.; Costa M.O.; Ribeiro M.O.; Okamoto M.M.; Lohmann T.H.; Machado U.F.; Musaro A.; Moriscot A.S.

Muscle IGF-1-induced skeletal muscle hypertrophy evokes higher insulin sensitivity and carbohydrate use as preferential energy substrate

Tipo

Artigo

Data de publicação

2015

Periódico

BioMed Research International

Citações (Scopus)

18

Autores

Christoffolete M.A.
Silva W.J.
Ramos G.V.
Bento M.R.
Costa M.O.
Ribeiro M.O.
Okamoto M.M.
Lohmann T.H.
Machado U.F.
Musaro A.
Moriscot A.S.

Resumo

© 2015 Marcelo Augusto Christoffolete et al.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.

Assuntos Scopus

Animals , Carbohydrate Metabolism , Glucose Transporter Type 4 , Hypertrophy , Insulin , Insulin Resistance , Insulin-Like Growth Factor I , Mice , Mice, Transgenic , Mitochondria , Muscle Proteins , Muscle, Skeletal , Peroxisome Proliferator-Activated Receptors , RNA, Messenger , Transcription Factors