Different Metabolism and Toxicity of TRANS Fatty Acids, Elaidate and Vaccenate Compared to Cis‐Oleate in Hepg2 Cells

Abstract

Trans fatty acids (TFAs) are not synthesized in the human body but are generally ingested in substantial amounts. The widespread view that TFAs, particularly those of industrial origin, are unhealthy and contribute to obesity, cardiovascular diseases and diabetes is based mostly on in vivo studies, and the underlying molecular mechanisms remain to be elucidated. Here, we used a hepa-toma model of palmitate‐induced lipotoxicity to compare the metabolism and effects of the repre-sentative industrial and ruminant TFAs, elaidate and vaccenate, respectively, with those of cis‐ole-ate. Cellular FAs, triacylglycerols, diacylglycerols and ceramides were quantitated using chroma-tography, markers of stress and apoptosis were assessed at mRNA and protein levels, ultrastruc-tural changes were examined by electron microscopy and viability was evaluated by MTT assay. While TFAs were just slightly more damaging than oleate when applied alone, they were remarka-bly less protective against palmitate toxicity in cotreatments. These differences correlated with their diverse incorporation into the accumulating diacylglycerols and ceramides. Our results provide in vitro evidence for the unfavorable metabolic features and potent stress‐inducing character of TFAs in comparison with oleate. These findings strengthen the reasoning against dietary trans fat intake, and they can also help us better understand the molecular mechanisms of lipotoxicity.