Figure 5 - available via license: Creative Commons Attribution 4.0 International
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Triglyceride content of hepatoma cells in lipotoxicity. Cells were treated with BSAconjugated palmitate, oleate, elaidate or vaccenate (800 µM) or with palmitate (800 µM) and oleate, elaidate or vaccenate at 4:1 or 2:1 molar ratio (200 or 400 µM) at 70-80% confluence for 8 h. The amount of relevant triglycerides (columns) was measured by LC-MS/MS. Data were normalized to the total protein content of the samples and are shown as the mean values of four independent experiments (see the mean and S.D. values in Table S6). The ratio of the mean values for fully saturated types (TG 16:0_16:0_16:0, TG 16:0_16:0_18:0, TG 16:0_18:0_18:0 and TG 18:0_18:0_18:0) and those containing at least two unsaturated chains (TG 16:0_18:1_18:1, TG 18:0_18:1_18:1 and TG 18:1_18:1_18:1) was calculated for each treatment (full circles connected with a continuous line for better visibility, right axis).
Source publication
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...
Contexts in source publication
Context 1
... reduction of the FA content in the incubation medium was assessed by GC-FID analysis. Each administered FA was effectively consumed from the medium, the drop in the concentrations was similar in all cases and more than 25% of the initial value during the 8 h long incubations ( Figure S5). The cell-derived FAs appeared again in the supernatant, but their concentration remained below 20 µM ( Figure S5). ...
Context 2
... administered FA was effectively consumed from the medium, the drop in the concentrations was similar in all cases and more than 25% of the initial value during the 8 h long incubations ( Figure S5). The cell-derived FAs appeared again in the supernatant, but their concentration remained below 20 µM ( Figure S5). ...
Context 3
... to our expectations, the applied FA supplementations triggered fat deposition in the hepatoma cells. Although palmitate alone caused a remarkable, nearly 4-fold increase in the overall TG level, the investigated cis or trans unsaturated FAs induced a much greater, more than 10-fold elevation in single supplementations ( Figure 5 and Figure S7-columns). The composition of accumulating fat was markedly different from the control. ...
Context 4
... the cells were incubated with the combination of palmitate and any of the unsaturated FAs, the overall TG content grew higher than in the palmitate treated cells, and, at a 2:1 ratio at 8 h, grew as high or even higher than on the corresponding unsaturated FA. Importantly, the fat composition in these cells, i.e., the ratio of fully saturated types (TG 16:0_16:0_16:0, TG 16:0_16:0_18:0, TG 16:0_18:0_18:0 and TG 18:0_18:0_18:0) and those containing at least two unsaturated chains (TG 16:0_18:1_18:1, TG 18:0_18:1_18:1 and TG 18:1_18:1_18:1) was much more similar to the control ( Figure 5 and Figure S7-line, Table S6). ...
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Background: Non-alcoholic fatty liver disease (NAFLD) is defined as the most prevalent hepatic disorder that affects a significant population worldwide. There are several genes/proteins, involving in the modulation of NAFLD pathogenesis; sirtuin1 (SIRT1), TP53-inducible regulator gene (TIGAR), and autophagy-related gene 5 (Atg5) are considered a ch...
Citations
... 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 . ...
Overnutrition and genetic predisposition are major risk factors for various metabolic disorders. Stearoyl-CoA desaturase-1 (SCD1) plays a key role in these conditions by synthesizing unsaturated fatty acids (FAs), thereby promoting fat storage and alleviating lipotoxicity. Expression of SCD1 is influenced by various saturated and cis-unsaturated FAs, but the possible role of dietary trans FAs (TFAs) and SCD1 promoter polymorphisms in its regulations has not been addressed. Therefore, we aimed to investigate the impact of the two main TFAs, vaccenate and elaidate, and four common promoter polymorphisms (rs1054411, rs670213, rs2275657, rs2275656) on SCD1 expression in HEK293T and HepG2 cell cultures using luciferase reporter assay, qPCR and immunoblotting. We found that SCD1 protein and mRNA levels as well as SCD1 promoter activity are markedly elevated by elaidate, but not altered by vaccenate. The promoter polymorphisms did not affect the basal transcriptional activity of SCD1. However, the minor allele of rs1054411 increased SCD1 expression in the presence of various FAs. Moreover, this variant was predicted in silico and verified in vitro to reduce the binding of ETS1 transcription factor to SCD1 promoter. Although we could not confirm an association with type 2 diabetes mellitus, the FA-dependent and ETS1-mediated effect of rs1054411 polymorphism deserves further investigation as it may modulate the development of lipid metabolism-related conditions.
... The most advanced trial is of the gemcitabine-elaidate prodrug (CP-4126), which has entered clinical trials for the treatment of pancreatic adenocarcinoma (NCT01124786). However, it is questionable why elaidate was used instead of oleate despite its unfavourable metabolic features and potent stress-induction of trans fatty acids compared to oleate 110 . ...
A low intake of ruminant trans fatty acids in the daily diet of Chinese residents exhibits salutary effects on health.
Dysregulation of lipid metabolism results in metabolism-related diseases. Our previous research indicated that 1.3% E and 4% E ruminant trans fatty acids (R-TFA) caused dyslipidemia and promoted atherosclerotic plaques in ApoE-/- mice, presenting detrimental effects. However, the effect of R-TFA on the lipid metabolism of normal mice remains unclear. Therefore, our current research aims to explore the effects of butter-derived R-TFAs on the lipid metabolism of C57BL/6J mice through the integration of lipidomics and transcriptomics. As a result, we found that 1.3% E butter-derived R-TFA promoted dyslipidemia and impaired hepatic function in C57BL/6J mice fed a high-fat diet, which was associated with an increase in DG (18:1/22:5), TG (18:1/18:2/22:4) and FA (24:5) as determined through lipidomics analysis, but had a less significant effect on C57BL/6J mice fed a low-fat diet. Through a combination analysis and verification of gene expression, we found that the arachidonic acid pathway might be involved in the disruption of lipid metabolism by butter-derived R-TFA. In addition, butter-derived R-TFA up-regulated the expression of unigene thromboxane-A synthase 1 (Tbxas1), arachidonate lipoxygenase 3 (Aloxe3), acyl-coenzyme A thioesterase 2 (Acot2), epoxide hydrolase 2 (Ephx2) and carbonyl reductase 3 (Cbr3) in C57BL/6J mice fed a high-fat diet. Herein, our research provides a new perspective for exploring the effects of butter-derived R-TFA on lipid metabolism and speculates on the possible mechanism of lipid metabolism disorder induced by butter-derived R-TFA in C57BL/6J mice fed a high-fat diet.