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Figure 3: PGC-1α-NCoRs antagonism controls insulin sensitivity in metabolic tissues. In adipose and skeletal muscle, the transcriptional activity of PPARγ and ERRα is responsible for the expression of gene networks that control glucose uptake, glycolysis, fatty acid oxidation, TCA cycle, OXPHOS, mitochondrial biogenesis, and uncoupling. Therefore, exercise and calorie restriction prevent obesity and insulin resistance probably by depressing NCoRs and increasing PGC-1α. PPARγ, peroxisome proliferator-activated receptor gamma; PGC-1α: PPARgamma coactivator 1-alpha; ERRα, Estrogen-related receptor alpha; RIP140: the corepressor receptor-interacting protein 140; NCoR: nuclear corepressor; SMRT: silencing mediator of retinoid and thyroid hormone receptors; HDAC3: Histone deacetylases 3; TG: Triglyceride; UCPs: uncoupling proteins; Mfn2: mitofusin 2; TIMM13: mitochondrial import inner membrane translocase subunit Tim13; OXPHOS: oxidative phosphorylation.