Cellular toxicity of dietary trans fatty acids and its correlation with ceramide and diglyceride accumulation

Sarnyai, Farkas; Donkó, Mária Berinkeiné; Mátyási, Judit; Gór-Nagy, Zsófia; Marczi, Ildikó; Simon-Szabó, Laura; Zámbó, Veronika; Somogyi, Anna; Csizmadia, Tamás; Lőw, Péter; Szelényi, Péter; Kereszturi, Éva; Tóth, Blanka; Csala, Miklós

doi:10.1016/j.fct.2018.12.022

Cited by 21 publications

(26 citation statements)

References 36 publications

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“…Therefore, the optimal palmitate concentration was high enough to challenge SCD1 enzyme, yet low enough to avoid lipotoxicity. A 50 µ m palmitate concentration was chosen based on previous findings in the literature and on our own experience with HEK293T and other cell lines . Our data support that this concentration was suitable to induce a significant change in the FA profile of HEK293T cells without any sign of derangement in cell viability or in metabolic balance.…”

Section: Discussionsupporting

confidence: 65%

“…Excessive fatty acid (FA) supply causes disturbance in the cellular signaling and metabolic functions, which can culminate in severe cell damage or even cell death . It has been repeatedly demonstrated that saturated FAs (e.g., palmitate) are far more deleterious than the endogenous cis‐unsaturated FAs (e.g., oleate) or even the dietary trans‐unsaturated FAs (e.g., elaidate and vaccenate) . Moreover, the damage caused by palmitate is often attenuated by simultaneously administered unsaturated FAs .…”

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confidence: 99%

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Investigation of the putative rate‐limiting role of electron transfer in fatty acid desaturation using transfected HEK293T cells

et al. 2019

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Elevated fatty acid (FA) levels contribute to severe metabolic diseases. Unbalanced oversupply of saturated FAs is particularly damaging, which renders stearoyl‐CoA desaturase (SCD1) activity an important factor of resistance. A SCD1‐related oxidoreductase protects cells against palmitate toxicity, so we aimed to test whether desaturase activity is limited by SCD1 itself or by the associated electron supply. Unsaturated/saturated FA ratio was markedly elevated by SCD1 overexpression while it remained unaffected by the overexpression of SCD1‐related electron transfer proteins in HEK293T cells. Electron supply was not rate‐limiting either in palmitate‐treated cells or in cells with enhanced SCD1 expression. Our findings indicate the rate‐limiting role of SCD1 itself, and that FA desaturation cannot be facilitated by reinforcing the electron supply of the enzyme.

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Section: Discussionsupporting

confidence: 65%

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confidence: 99%

Investigation of the putative rate‐limiting role of electron transfer in fatty acid desaturation using transfected HEK293T cells

et al. 2019

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“…Most importantly, it has been shown that co-administration of oleate can prevent palmitate-induced activation of the unfolded protein response (UPR) in β-cells [19]. In light of our recent observations [16], we find it intriguing if dietary TFAs are also protective like cis-oleate when added to the cells together with palmitate.…”

Section: Introductionmentioning

confidence: 79%

“…We have recently compared the effects and metabolism of the two major dietary TFAs, i.e., elaidate (18:1 trans-∆9) of industrial origin and vaccenate (18:1 trans-∆11) derived from natural sources, with those of palmitate and oleate in RINm5F rat insulinoma cells. It has been demonstrated that the toxicity of both TFAs were much lower than that of palmitate and similar to that of oleate, which correlated well with the marked accumulation of ceramides and diglycerides (DGs) in palmitate-treated cells and with the mild elevation in ceramide and DG levels upon the administration of cis-or trans-unsaturated FAs [16].…”

Section: Introductionmentioning

confidence: 88%

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

Sarnyai

Somogyi

Gór-Nagy

et al. 2020

IJMS

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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.

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The role of sphingolipids in endoplasmic reticulum stress

Park

2020

FEBS Letters

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The endoplasmic reticulum (ER) is an important intracellular compartment in eukaryotic cells and has diverse functions, including protein synthesis, protein folding, lipid metabolism and calcium homeostasis. ER functions are disrupted by various intracellular and extracellular stimuli that cause ER stress, including the inhibition of glycosylation, disulphide bond reduction, ER calcium store depletion, impaired protein transport to the Golgi, excessive ER protein synthesis, impairment of ER-associated protein degradation and mutated ER protein expression. Distinct ER stress signalling pathways, which are known as the unfolded protein response, are deployed to maintain ER homeostasis, and a failure to reverse ER stress triggers cell death. Sphingolipids are lipids that are structurally characterized by long-chain bases, including sphingosine or dihydrosphingosine (also known as sphinganine). Sphingolipids are bioactive molecules long known to regulate various cellular processes, including cell proliferation, migration, apoptosis and cell-cell interaction. Recent studies have uncovered that specific sphingolipids are involved in ER stress. This review summarizes the roles of sphingolipids in ER stress and human diseases in the context of pathogenic events.

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Cellular toxicity of dietary trans fatty acids and its correlation with ceramide and diglyceride accumulation

Cited by 21 publications

References 36 publications

Investigation of the putative rate‐limiting role of electron transfer in fatty acid desaturation using transfected HEK293T cells

Investigation of the putative rate‐limiting role of electron transfer in fatty acid desaturation using transfected HEK293T cells

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

The role of sphingolipids in endoplasmic reticulum stress

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