Department of Molecular Biology, Semmelweis University, H-1094 Budapest, Hungary.
Department of Inorganic and Analytical Chemistry, Budapest University of Technology and Economics, H-1111 Budapest, Hungary.
Int J Mol Sci. 2022 Jun 30;23(13):7298. doi: 10.3390/ijms23137298.
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.
反式脂肪酸（TFAs）在人体内不能合成，但通常会大量摄入。人们普遍认为，TFAs，特别是那些工业来源的 TFAs，对健康有害，会导致肥胖、心血管疾病和糖尿病，这种观点主要基于体内研究，其潜在的分子机制仍有待阐明。在这里，我们使用棕榈酸诱导的脂肪毒性肝癌模型，分别比较了代表性的工业反式脂肪酸（elaidate）和反刍动物反式脂肪酸（vaccenate）与顺式油酸的代谢和作用。采用色谱法定量检测细胞脂肪酸、三酰甘油、二酰甘油和神经酰胺，用 mRNA 和蛋白质水平评估应激和细胞凋亡的标志物，用电镜检查超微结构变化，用 MTT 法评估细胞活力。虽然 TFAs 单独使用时的损伤程度略高于油酸，但在与棕榈酸的共同处理中，它们对棕榈酸毒性的保护作用明显降低。这些差异与它们在不断积累的二酰甘油和神经酰胺中的不同掺入有关。我们的研究结果为 TFAs 与油酸相比在代谢特征和应激诱导方面的不利特征提供了体外证据。这些发现加强了反对饮食中摄入反式脂肪的理由，也有助于我们更好地理解脂肪毒性的分子机制。
