miR-222 is involved in the regulation of genistein on skeletal muscle fiber type

J Nutr Biochem. 2020 Jun:80:108320. doi: 10.1016/j.jnutbio.2019.108320. Epub 2019 Dec 11.

Abstract

In skeletal muscle, the composition of the fiber types has a profound impact on athletic performance, such as endurance or strength output. The proportions of muscle fiber types have also been associated with certain diseases, including dyskinesia, obesity and insulin resistance. Genistein, a natural estrogen, has been demonstrated to regulate fatty acid oxidation and insulin sensitivity in skeletal muscle. However, it is unknown whether genistein can regulate skeletal muscle fiber types. Furthermore, the mechanism of its effect on skeletal muscle energy metabolism is not entirely clear. In this study, in vivo and in vitro experiments were used to explore the effect of genistein on the muscle fiber-type transitions and muscle metabolism. The results indicated that genistein not only promotes skeletal muscle development but increases the expression of slow muscle fibers in mice as well. It was also demonstrated that genistein altered the ratios of fiber type and promoted mitochondrial biogenesis in C2C12 myoblasts. Interestingly, the expression of miR-222 was decreased by genistein, and it was demonstrated that this microRNA targets the PGC1α gene. In C2C12 myoblasts, miR-222 appears to regulate fiber type conversion and mitochondrial biogenesis. However, this function was significantly reduced following genistein treatment. These results suggest that miR-222 may be involved in the regulation of genistein on skeletal muscle fiber and muscle metabolism, and genistein may be used to improve muscle health.

Keywords: Genistein; Mitochondria; Muscle fiber; Muscle metabolism; miR-222.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Estrogen Receptor alpha / metabolism
  • Female
  • Genistein / pharmacology*
  • Mice
  • MicroRNAs / metabolism*
  • Mitochondria / metabolism
  • Muscle Development / drug effects
  • Muscle Fibers, Skeletal / drug effects
  • Muscle Fibers, Skeletal / metabolism*
  • Muscle, Skeletal / metabolism
  • MyoD Protein / metabolism
  • Myoblasts / metabolism
  • Organelle Biogenesis
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism
  • Signal Transduction

Substances

  • Esr1 protein, mouse
  • Estrogen Receptor alpha
  • MIRN222 microRNA, mouse
  • MicroRNAs
  • MyoD Protein
  • MyoD1 myogenic differentiation protein
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Genistein