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 hepatoma model of palmitate-induced lipotoxicity to compare the metabolism and effects of the representative industrial and ruminant TFAs, elaidate and vaccenate, respectively, with those of cis-oleate. Cellular FAs, triacylglycerols, diacylglycerols and ceramides were quantitated using chromatography, markers of stress and apoptosis were assessed at mRNA and protein levels, ultrastructural 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 remarkably 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.

Allele-specific effect of various dietary fatty acids and ETS1 transcription factor on SCD1 expression

“…Although oleate clearly decreases the desaturase the level of the enzyme and thus the desaturase activity, there are inconsistent findings with respect to the effect at the mRNA level, and even more so with respect to the promoter activity, suggesting that oleate acts through mRNA and/or protein stabilization rather than reducing transcription 33 . It should be noted that the well-characterized reducing effect of oleate on SCD1 was not seen at all three regulatory levels we examined in HepG2 cells, and the effect of other FAs was also rather modest in this cell line, probably due to the relatively high FA tolerance of HepG2 cells 34 .…”

Low intake of ruminant trans fatty acids ameliorates the disordered lipid metabolism in C57BL/6J mice fed a high-fat diet

“…2,3 A large number of investigations suggest that TFA adversely disrupt organism homeostasis and promote the progression of metabolism-related diseases, such as diabetes, non-alcoholic fatty liver diseases (NAFLD), obesity, and cardiovascular diseases (CVD). [4][5][6][7] Therefore, efforts have been made in the past decade to remove TFA from dietary foods, and it has been authorized that TFA intake should be restricted to lower than 1% of the total energy requirement from food. Since then, the worldwide consumption of TFA has decreased remarkably, from an average of 10 g d −1 (about 4.0% of the total energy requirement in a 2250 kcal diet) to 3-4 g d −1 in North America, 2-4 g d −1 in Nordic countries, 1-3 g d −1 in Mediterranean countries and less than 1 g d −1 in some Asian countries.…”

Integration of hepatic lipidomics and transcriptomics reveals the effect of butter-derived ruminant trans fatty acids on lipid metabolism in C57BL/6J mice

“…1,2 I-TFA are formed in greater quantity by elaidic acid (EA), while R-TFA are mainly represented by trans vaccenic acid (TVA) and trans palmitoleic acid (TPA). Currently, more and more epidemiological and clinical studies have confirmed that I-TFA are associated with the emergence and progression of metabolism-related diseases, [3][4][5] including cardiovascular diseases, 1,6 diabetes 7 and cancer. [8][9][10] In contrast to I-TFA, the health effects of R-TFA are still controversial.…”

“…[16][17][18] By using lipidomics, Sarnyai et al suggested that EA and TVA induced a stress response and cell damage in HepG2 cells by increasing the levels of ceramide (Cer) and diglyceride (DG), and this further supported the role of DG and Cer accumulation in metabolic diseases. 3 Hepatic steatosis, non-alcoholic steatohepatitis (NASH) and liver fibrosis are the three stages of increasing severity in NAFLD, which can even deteriorate toward cirrhosis and hepatocellular carcinoma. 19 Oii and colleagues used hepatic lipidomics techniques to screen for underlying biomarkers during the progression of non-alcoholic fatty liver disease (NAFLD) and found that Cer, DG, and TG were significantly increased in hepatic lipids in NAFLD.…”