Obestatin controls skeletal muscle fiber-type determination

Sci Rep. 2017 May 18;7(1):2137. doi: 10.1038/s41598-017-02337-4.

Abstract

Obestatin/GPR39 signaling stimulates skeletal muscle growth and repair by inducing both G-protein-dependent and -independent mechanisms linking the activated GPR39 receptor with distinct sets of accessory and effector proteins. In this work, we describe a new level of activity where obestatin signaling plays a role in the formation, contractile properties and metabolic profile of skeletal muscle through determination of oxidative fiber type. Our data indicate that obestatin regulates Mef2 activity and PGC-1α expression. Both mechanisms result in a shift in muscle metabolism and function. The increase in Mef2 and PGC-1α signaling activates oxidative capacity, whereas Akt/mTOR signaling positively regulates myofiber growth. Taken together, these data indicate that the obestatin signaling acts on muscle fiber-type program in skeletal muscle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Ghrelin / pharmacology*
  • MEF2 Transcription Factors / metabolism
  • Male
  • Mice
  • Muscle Development / drug effects*
  • Muscle Fibers, Skeletal / cytology
  • Muscle Fibers, Skeletal / drug effects
  • Muscle Fibers, Skeletal / metabolism*
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Receptors, G-Protein-Coupled / metabolism
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • GPR39 protein, mouse
  • Ghrelin
  • MEF2 Transcription Factors
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, mouse
  • Receptors, G-Protein-Coupled
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases