Effect of cis- and trans-Monounsaturated Fatty Acids on Palmitate Toxicity and on Palmitate-induced Accumulation of Ceramides and Diglycerides

Int J Mol Sci. 2020 Apr 9;21(7):2626. doi: 10.3390/ijms21072626.

Abstract

Dietary trans fatty acids (TFAs) have been implicated in serious health risks, yet little is known about their cellular effects and metabolism. We aim to undertake an in vitro comparison of two representative TFAs (elaidate and vaccenate) to the best-characterized endogenous cis-unsaturated FA (oleate). The present study addresses the possible protective action of TFAs on palmitate-treated RINm5F insulinoma cells with special regards to apoptosis, endoplasmic reticulum stress and the underlying ceramide and diglyceride (DG) accumulation. Both TFAs significantly improved cell viability and reduced apoptosis in palmitate-treated cells. They mildly attenuated palmitate-induced XBP-1 mRNA cleavage and phosphorylation of eukaryotic initiation factor 2α (eIF2α) and stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK), but they were markedly less potent than oleate. Accordingly, all the three unsaturated FAs markedly reduced cellular palmitate incorporation and prevented harmful ceramide and DG accumulation. However, more elaidate or vaccenate than oleate was inserted into ceramides and DGs. Our results revealed a protective effect of TFAs in short-term palmitate toxicity, yet they also provide important in vitro evidence and even a potential mechanism for unfavorable long-term health effects of TFAs compared to oleate.

Keywords: ceramide; diabetes; diacylglycerol; endoplasmic reticulum stress; lipotoxicity; trans fatty acid.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Line
  • Cell Survival / drug effects
  • Ceramides / metabolism*
  • Diglycerides / metabolism*
  • Dose-Response Relationship, Drug
  • Endoplasmic Reticulum Stress / drug effects
  • Fatty Acids, Monounsaturated / chemistry
  • Fatty Acids, Monounsaturated / pharmacology*
  • Lipid Metabolism / drug effects*
  • Palmitates / adverse effects*
  • Rats

Substances

  • Ceramides
  • Diglycerides
  • Fatty Acids, Monounsaturated
  • Palmitates