Increased oxidative stress and mitochondrial impairments associated with increased expression of TNF-α and caspase-3 in palmitic acid-induced lipotoxicity in myoblasts

J Biochem Mol Toxicol. 2021 May;35(5):e22744. doi: 10.1002/jbt.22744. Epub 2021 Feb 18.

Abstract

Saturated fatty acids, whose circulating levels are markedly increased in the body, significantly affect the growth and functions of skeletal muscle. These fatty acids may exert a detrimental effect on the undifferentiated skeletal myoblasts that may adversely affect their differentiation. In the present study, the exposure of myoblasts to excess palmitic acid caused an elevation of tumor necrosis factor-α expression and an increase in reactive oxygen species levels consistent with the enhanced inflammation and oxidative stress. Various concentrations of palmitic acid significantly decreased the mitochondrial membrane potential, induced the programmed cell death by an increase in the caspase-3 expression, and DNA fragmentation in the myoblasts. These findings suggest that the increased concentrations of saturated fatty acid in the myoblasts increase lipotoxicity by increasing inflammation and oxidative stress, decreasing the mitochondrial function, and inducing apoptosis.

Keywords: apoptosis; mitochondrial membrane potential; myoblast; reactive oxygen species; saturated fatty acid.

MeSH terms

  • Caspase 3 / biosynthesis*
  • Cell Line
  • DNA Fragmentation / drug effects
  • Gene Expression Regulation / drug effects*
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria, Muscle / metabolism*
  • Mitochondria, Muscle / pathology
  • Myoblasts / metabolism*
  • Myoblasts / pathology
  • Oxidative Stress / drug effects*
  • Palmitic Acid / toxicity*
  • Tumor Necrosis Factor-alpha / biosynthesis*

Substances

  • Tumor Necrosis Factor-alpha
  • Palmitic Acid
  • CASP3 protein, human
  • Caspase 3