Cellular toxicity of dietary trans fatty acids and its correlation with ceramide and diglyceride accumulation

Food Chem Toxicol. 2019 Feb:124:324-335. doi: 10.1016/j.fct.2018.12.022. Epub 2018 Dec 17.

Abstract

High fatty acid (FA) levels are deleterious to pancreatic β-cells, largely due to the accumulation of biosynthetic lipid intermediates, such as ceramides and diglycerides, which induce ER stress and apoptosis. Toxicity of palmitate (16:0) and oleate (18:1 cis-Δ9) has been widely investigated, while very little data is available on the cell damages caused by elaidate (18:1 trans-Δ9) and vaccenate (18:1 trans-Δ11), although the potential health effects of these dietary trans fatty acids (TFAs) received great publicity. We compared the effects of these four FAs on cell viability, apoptosis, ER stress, JNK phosphorylation and autophagy as well as on ceramide and diglyceride contents in RINm5F insulinoma cells. Similarly to oleate and unlike palmitate, TFAs reduced cell viability only at higher concentration, and they had mild effects on ER stress, apoptosis and autophagy. Palmitate increased ceramide and diglyceride levels far more than any of the unsaturated fatty acids; however, incorporation of TFAs in ceramides and diglycerides was strikingly more pronounced than that of oleate. This indicates a correlation between the accumulation of lipid intermediates and the severity of cell damage. Our findings reveal important metabolic characteristics of TFAs that might underlie a long term toxicity and hence deserve further investigation.

Keywords: Apoptosis; Ceramide; Diabetes; Diglyceride; Endoplasmic reticulum stress; Trans fatty acids.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Ceramides / metabolism*
  • Dietary Fats, Unsaturated / analysis
  • Dietary Fats, Unsaturated / toxicity*
  • Diglycerides / metabolism*
  • Endoplasmic Reticulum Stress / drug effects
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / pathology
  • MAP Kinase Kinase 4 / metabolism
  • Necrosis / chemically induced
  • Oleic Acid / analysis
  • Oleic Acid / toxicity*
  • Oleic Acids / analysis
  • Oleic Acids / toxicity*
  • Palmitic Acids / analysis
  • Palmitic Acids / toxicity
  • Phosphorylation
  • Rats
  • Trans Fatty Acids / analysis
  • Trans Fatty Acids / toxicity*

Substances

  • Ceramides
  • Dietary Fats, Unsaturated
  • Diglycerides
  • Oleic Acids
  • Palmitic Acids
  • Trans Fatty Acids
  • Oleic Acid
  • elaidic acid
  • MAP Kinase Kinase 4
  • 11-octadecenoic acid