Road to exercise mimetics: targeting nuclear receptors in skeletal muscle

  1. Ronald M Evans1,2
  1. 1Gene Expression Laboratory
    2Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, California 92037, USA
  1. Correspondence should be addressed to R M Evans; Email: evans{at}
  1. Figure 1

    NR regulation of energy metabolism and remodeling in skeletal muscle. The NR ring of physiology is shown on the left (Bookout et al. 2006). It clusters 49 mouse NRs into six groups based on their tissue distribution patterns. The NRs that have been found to play crucial roles in skeletal muscle function (highlighted in red/bold) are clustered mainly in two groups: group IC, the members of which are selectively expressed in highly metabolic tissues and are involved in CNS, circadian, and basal metabolic functions, including NOR1, NUR77, NURR1, ERRβ, ERRγ, REV-ERBα, and REV-ERBβ, and groups IIB and IIC, the members of which are broadly expressed and are linked to lipid metabolism and energy homeostasis, including PPARα, PPARδ, PPARγ, and ERRα. These NRs work in concert with exercise and co-regulators to regulate many aspects of skeletal muscle physiology. Synthetic ligands targeting NRs and their co-regulators can enhance or replace the physiological benefits induced by exercise, which is of great value to public health.

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