Palmitate exerts opposite effects on proliferation and differentiation of skeletal myoblasts

Cell Biol Int. 2015 Sep;39(9):1044-52. doi: 10.1002/cbin.10477. Epub 2015 May 20.

Abstract

The purpose of the study was to examine mechanisms controlling cell cycle progression/arrest and differentiation of mouse C2C12 myoblasts exposed to long-chain saturated fatty acid salt, palmitate. Treatment of proliferating myoblasts with palmitate (0.1 mmol/l) markedly decreased myoblast number. Cyclin A and cyclin D1 levels decreased, whereas total p21 and p21 complexed with cyclin-dependent kinase-4 (cdk4) increased in myoblasts treated with palmitate. In cells induced to differentiation addition of palmitate augmented the level of cyclin D3, the early (myogenin) and late (α-actinin, myosin heavy chain) markers of myogenesis, and caused an increase of myotube diameter. In conclusion, exposure to palmitate inhibits proliferation of myoblasts through a decrease in cyclin A and cyclin D1 levels and an increase of p21-cdk4 complex formation; however, it promotes cell cycle exit, myogenic differentiation and myotube growth.

Keywords: G1 cyclins; long-chain fatty acids; myogenesis; myogenic regulatory factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle / drug effects
  • Cell Differentiation / drug effects
  • Cell Line
  • Cell Proliferation / drug effects
  • Cyclin A / drug effects
  • Cyclin D1 / drug effects
  • Cyclin-Dependent Kinase 4 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21
  • Mice
  • Muscle Fibers, Skeletal / drug effects
  • Myoblasts, Skeletal / cytology
  • Myoblasts, Skeletal / drug effects*
  • Myoblasts, Skeletal / metabolism
  • Myogenin / drug effects
  • Palmitates / pharmacology*

Substances

  • Cyclin A
  • Cyclin-Dependent Kinase Inhibitor p21
  • Myogenin
  • Palmitates
  • Cyclin D1
  • Cdk4 protein, mouse
  • Cyclin-Dependent Kinase 4