Saturated fatty acid palmitate-induced insulin resistance is accompanied with myotube loss and the impaired expression of health benefit myokine genes in C2C12 myotubes

Lipids Health Dis. 2013 Jul 18;12:104. doi: 10.1186/1476-511X-12-104.

Abstract

Background: Excessive circular fatty acid, particlarly saturated fatty acid, can result in insulin resistance in skeletal muscle, but other adverse effects of fatty acid accumulation in myocytes remain unclear.

Methods: Differentiated C2C12 myotubes were used. The effects of palmitate on cell viability, glucose uptake, gene expression and myotube loss were evaluated by MTT assay, 2NBDG uptake, qRT-PCR, Western Blot and crystal staining-based myotube counting, respectively. In some expreiments, oleate was administrated, or the inhibitors of signaling pathways were applied.

Results: Palmitate-induced cellular insulin resistance was clarified by the reduced Akt phosphorylation, glucose uptake and Glut4 expression. Palmitate-caused myotube loss was clearly observed under microscope and proved by myotube counting and expression analysis of myotube marker genes. Moreover, palmitate-induced transcriptional suppression of three health benefit myokine genes (FNDC5, CTRP15 and FGF21) was found, and the different involvement of p38 and PI3K in the transcription of these genes was noticed.

Conclusions: Palmitate-induced insulin resistance accompanys myotube loss and the impaired expression of FNDC5, CTRP15 and FGF21genes in C2C12 myotubes. These results provide novel evidence indicating the negative role of high concentration of palmitate in myotubes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Culture Techniques
  • Cell Survival / drug effects*
  • Cytokines / biosynthesis
  • Fatty Acids / administration & dosage
  • Fatty Acids / metabolism
  • Fibroblast Growth Factors / biosynthesis
  • Fibronectins / biosynthesis
  • Gene Expression Regulation / drug effects
  • Glucose Transporter Type 4 / biosynthesis
  • Insulin Resistance*
  • Mice
  • Muscle Fibers, Skeletal / drug effects
  • Muscle Proteins / biosynthesis
  • Muscle, Skeletal / drug effects*
  • Palmitates / administration & dosage*
  • Palmitates / metabolism

Substances

  • CTRP15 protein, mouse
  • Cytokines
  • FNDC5 protein, mouse
  • Fatty Acids
  • Fibronectins
  • Glucose Transporter Type 4
  • Muscle Proteins
  • Palmitates
  • Slc2a4 protein, mouse
  • fibroblast growth factor 21
  • Fibroblast Growth Factors