The effect of exercise on epigenetic modifications of PGC1: The impact on type 2 diabetes.
The worldwide prevalence of diabetes type 2 is increasing and intramuscular accumulation of fatty acid metabolites is gradually becoming recognized as core features of this condition as lipotoxicity induces insulin resistance. Emerging evidences suggest that defects in mitochondria, key organelle in lipid metabolism, play a central role on insulin resistance. Mitochondria homeostasis is tightly regulated by a nucleus-mitochondria signaling pathway and peroxisome proliferator-activated receptor γ coactivator-1α (PGC1) is the master regulator of important mitochondria process. PGC1 is down regulated in insulin resistant skeletal muscle and abnormal posttranslational modification at histone, epigenetic modifications, is an important factor. Studies have demonstrated the benefits of regular exercise on improving insulin sensitivity however the mechanism for this outcome is not entirely identified. Moreover evidences point out the increase in PGC1 expression induced by exercise as an important element for the improvement of insulin sensitivity in skeletal muscle via increase in mitochondria density and glucose transporter expression (GLUT4). Therefore, we here proposed that aerobic exercise attenuates epigenetic modifications at PGC1 induced by high-energy diets and reduced physical activity, and that leads to inhibition/delay of type 2 diabetic onset.
Wayne State University, Detroit R&D, Detroit, MI, USA; Federal University of Goiás, CAJ, Jataí, Brazil. Electronic address: Julia.santos@wayne.edu.
Júlia M
JM
Santos
Ram Manohar Lohia, Institute of Medical Science, Lucknow, India.
Shikha
S
Tewari
Federal University of Goiás, CAJ, Jataí, Brazil.
Sandra A
SA
Benite-Ribeiro
D004268:DNA-Binding Proteins / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D044127:Epigenesis, Genetic / Q000235:genetics / Q000502:physiology*; D015444:Exercise / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C480633:SLC2A4RG protein, human; D014157:Transcription Factors