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data reveal that a PPARδ-mediated transcriptional pathway can regulate muscle fiber specification, enabling the generation of a strain of mice with a “long-distance running” phenotype. We show that targeted expression of an activated form of PPARδ produces profound and coordinated increases in oxidation enzymes, mitochondrial biogenesis, and production of specialized type I fiber contractile proteins—the three hallmarks for muscle fiber type switching (Figure 6C). While induction of muscle oxidation enzymes by PPARδ has been seen both in vivo and in vitro (Muoio et al. 2002; Dressel et al. 2003; Luquet et al. 2003; Tanaka et al. 2003; Wang et al. 2003), its effects shown here on muscle fiber switching are unexpected. These progressive changes in oxidative capacity in conjunction with eventual changes in type I muscle fiber lead to a dramatically improved exercise profile and protection against obesity. This does not solely depend on achieving a directed muscle fiber type switch but also requires all the associated changes in neural innervation, motor neuron function, and peripheral metabolic adaptation to enable a new integrated physiological response. Accordingly, activation of muscle PPARδ essentially recapitulates the effects of exercise training even in the absence of training itself. To our knowledge, this has not been directly described for any other transcriptional factor."}

{"project":"2_test","denotations":[{"id":"15328533-12118038-84708281","span":{"begin":580,"end":584},"obj":"12118038"},{"id":"15328533-14525954-84708282","span":{"begin":601,"end":605},"obj":"14525954"},{"id":"15328533-14525942-84708283","span":{"begin":621,"end":625},"obj":"14525942"},{"id":"15328533-14676330-84708284","span":{"begin":641,"end":645},"obj":"14676330"},{"id":"15328533-12705865-84708285","span":{"begin":659,"end":663},"obj":"12705865"},{"id":"T88229","span":{"begin":580,"end":584},"obj":"12118038"},{"id":"T92978","span":{"begin":601,"end":605},"obj":"14525954"},{"id":"T44137","span":{"begin":621,"end":625},"obj":"14525942"},{"id":"T54414","span":{"begin":641,"end":645},"obj":"14676330"},{"id":"T67140","span":{"begin":659,"end":663},"obj":"12705865"}],"text":"Our data reveal that a PPARδ-mediated transcriptional pathway can regulate muscle fiber specification, enabling the generation of a strain of mice with a “long-distance running” phenotype. We show that targeted expression of an activated form of PPARδ produces profound and coordinated increases in oxidation enzymes, mitochondrial biogenesis, and production of specialized type I fiber contractile proteins—the three hallmarks for muscle fiber type switching (Figure 6C). While induction of muscle oxidation enzymes by PPARδ has been seen both in vivo and in vitro (Muoio et al. 2002; Dressel et al. 2003; Luquet et al. 2003; Tanaka et al. 2003; Wang et al. 2003), its effects shown here on muscle fiber switching are unexpected. These progressive changes in oxidative capacity in conjunction with eventual changes in type I muscle fiber lead to a dramatically improved exercise profile and protection against obesity. This does not solely depend on achieving a directed muscle fiber type switch but also requires all the associated changes in neural innervation, motor neuron function, and peripheral metabolic adaptation to enable a new integrated physiological response. Accordingly, activation of muscle PPARδ essentially recapitulates the effects of exercise training even in the absence of training itself. To our knowledge, this has not been directly described for any other transcriptional factor."}

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