| First Author | Gan Z | Year | 2013 |
| Journal | J Clin Invest | Volume | 123 |
| Issue | 6 | Pages | 2564-75 |
| PubMed ID | 23676496 | Mgi Jnum | J:201439 |
| Mgi Id | MGI:5514107 | Doi | 10.1172/JCI67652 |
| Citation | Gan Z, et al. (2013) Nuclear receptor/microRNA circuitry links muscle fiber type to energy metabolism. J Clin Invest 123(6):2564-75 |
| abstractText | The mechanisms involved in the coordinate regulation of the metabolic and structural programs controlling muscle fitness and endurance are unknown. Recently, the nuclear receptor PPARbeta/delta was shown to activate muscle endurance programs in transgenic mice. In contrast, muscle-specific transgenic overexpression of the related nuclear receptor, PPARalpha, results in reduced capacity for endurance exercise. We took advantage of the divergent actions of PPARbeta/delta and PPARalpha to explore the downstream regulatory circuitry that orchestrates the programs linking muscle fiber type with energy metabolism. Our results indicate that, in addition to the well-established role in transcriptional control of muscle metabolic genes, PPARbeta/delta and PPARalpha participate in programs that exert opposing actions upon the type I fiber program through a distinct muscle microRNA (miRNA) network, dependent on the actions of another nuclear receptor, estrogen-related receptor gamma (ERRgamma). Gain-of-function and loss-of-function strategies in mice, together with assessment of muscle biopsies from humans, demonstrated that type I muscle fiber proportion is increased via the stimulatory actions of ERRgamma on the expression of miR-499 and miR-208b. This nuclear receptor/miRNA regulatory circuit shows promise for the identification of therapeutic targets aimed at maintaining muscle fitness in a variety of chronic disease states, such as obesity, skeletal myopathies, and heart failure. |
