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Article ; Online: Allele-specific effect of various dietary fatty acids and ETS1 transcription factor on SCD1 expression.

Tibori, Kinga / Zámbó, Veronika / Orosz, Gabriella / Szelényi, Péter / Sarnyai, Farkas / Tamási, Viola / Rónai, Zsolt / Csala, Miklós / Kereszturi, Éva

Scientific reports

2024 Volume 14, Issue 1, Page(s) 177

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Humans ; Transcription Factors/genetics ; Diabetes Mellitus, Type 2/genetics ; Alleles ; HEK293 Cells ; Fatty Acids/metabolism ; Fatty Acids, Unsaturated ; Fatty Acids, Monounsaturated ; Stearoyl-CoA Desaturase/genetics ; Stearoyl-CoA Desaturase/metabolism ; Proto-Oncogene Protein c-ets-1/genetics
Chemical Substances	Transcription Factors ; Fatty Acids ; Fatty Acids, Unsaturated ; Fatty Acids, Monounsaturated ; Stearoyl-CoA Desaturase (EC 1.14.19.1) ; ETS1 protein, human ; Proto-Oncogene Protein c-ets-1 ; SCD1 protein, human (EC 1.14.19.1)
Language	English
Publishing date	2024-01-02
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-50700-5
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Article ; Online: High fat diet and PCSK9 knockout modulates lipid profile of the liver and changes the expression of lipid homeostasis related genes

Németh, Krisztina / Tóth, Blanka / Sarnyai, Farkas / Koncz, Anna / Lenzinger, Dorina / Kereszturi, Éva / Visnovitz, Tamás / Kestecher, Brachyahu Meir / Osteikoetxea, Xabier / Csala, Miklós / Buzás, Edit I. / Tamási, Viola

Nutr Metab (Lond). 2023 Dec., v. 20, no. 1 p.19-19

2023

Abstract: BACKGROUND: High fat diet (HFD) increases the likelihood of dyslipidemia, which can be a serious risk factor for atherosclerosis, diabetes or hepatosteatosis. Although changes in different blood lipid levels were broadly investigated, such alterations in ...

Abstract	BACKGROUND: High fat diet (HFD) increases the likelihood of dyslipidemia, which can be a serious risk factor for atherosclerosis, diabetes or hepatosteatosis. Although changes in different blood lipid levels were broadly investigated, such alterations in the liver tissue have not been studied before. The aim of the current study was to investigate the effect of HFD on hepatic triglyceride (TG), diglyceride (DG) and ceramide (CER) levels and on the expression of four key genes involved in lipid homeostasis (Pcsk9, Ldlr, Cd36 and Anxa2) in the liver. In addition, the potential role of PCSK9 in the observed changes was further investigated by using PCSK9 deficient mice. METHODS: We used two in vivo models: mice kept on HFD for 20 weeks and PCSK9⁻/⁻ mice. The amount of the major TGs, DGs and CERs was measured by using HPLC–MS/MS analysis. The expression profiles of four lipid related genes, namely Pcsk9, Ldlr, Cd36 and Anxa2 were assessed. Co-localization studies were performed by confocal microscopy. RESULTS: In HFD mice, hepatic PCSK9 expression was decreased and ANXA2 expression was increased both on mRNA and protein levels, and the amount of LDLR and CD36 receptor proteins was increased. While LDLR protein level was also elevated in the livers of PCSK9⁻/⁻ mice, there was no significant change in the expression of ANXA2 and CD36 in these animals. HFD induced a significant elevation in the hepatic levels of all measured TG and DG but not of CER types, and increased the proportion of monounsaturated vs. saturated TGs and DGs. Similar changes were detected in the hepatic lipid profiles of HFD and PCSK9⁻/⁻ mice. Co-localization of PCSK9 with LDLR, CD36 and ANXA2 was verified in HepG2 cells. CONCLUSIONS: Our results show that obesogenic HFD downregulates PCSK9 expression in the liver and causes alterations in the hepatic lipid accumulation, which resemble those observed in PCSK9 deficiency. These findings suggest that PCSK9-mediated modulation of LDLR and CD36 expression might contribute to the HFD-induced changes in lipid homeostasis.
Keywords	atherosclerosis ; blood lipids ; ceramides ; confocal microscopy ; diabetes ; diacylglycerols ; high fat diet ; homeostasis ; hyperlipidemia ; lipid composition ; liver ; protein content ; risk factors ; triacylglycerols
Language	English
Dates of publication	2023-12
Size	p. 19.
Publishing place	BioMed Central
Document type	Article ; Online
ZDB-ID	2160376-5
ISSN	1743-7075
ISSN	1743-7075
DOI	10.1186/s12986-023-00738-z
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Article: High fat diet and PCSK9 knockout modulates lipid profile of the liver and changes the expression of lipid homeostasis related genes.

Nutrition & metabolism

2023 Volume 20, Issue 1, Page(s) 19

Abstract: Background: High fat diet (HFD) increases the likelihood of dyslipidemia, which can be a serious risk factor for atherosclerosis, diabetes or hepatosteatosis. Although changes in different blood lipid levels were broadly investigated, such alterations ... ...

Abstract	Background: High fat diet (HFD) increases the likelihood of dyslipidemia, which can be a serious risk factor for atherosclerosis, diabetes or hepatosteatosis. Although changes in different blood lipid levels were broadly investigated, such alterations in the liver tissue have not been studied before. The aim of the current study was to investigate the effect of HFD on hepatic triglyceride (TG), diglyceride (DG) and ceramide (CER) levels and on the expression of four key genes involved in lipid homeostasis (Pcsk9, Ldlr, Cd36 and Anxa2) in the liver. In addition, the potential role of PCSK9 in the observed changes was further investigated by using PCSK9 deficient mice. Methods: We used two in vivo models: mice kept on HFD for 20 weeks and PCSK9 Results: In HFD mice, hepatic PCSK9 expression was decreased and ANXA2 expression was increased both on mRNA and protein levels, and the amount of LDLR and CD36 receptor proteins was increased. While LDLR protein level was also elevated in the livers of PCSK9 Conclusions: Our results show that obesogenic HFD downregulates PCSK9 expression in the liver and causes alterations in the hepatic lipid accumulation, which resemble those observed in PCSK9 deficiency. These findings suggest that PCSK9-mediated modulation of LDLR and CD36 expression might contribute to the HFD-induced changes in lipid homeostasis.
Language	English
Publishing date	2023-03-31
Publishing country	England
Document type	Journal Article
ZDB-ID	2160376-5
ISSN	1743-7075
ISSN	1743-7075
DOI	10.1186/s12986-023-00738-z
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Article ; Online: O-glycosylation sites identified from mucin core-1 type glycopeptides from human serum.

Darula, Zsuzsanna / Sarnyai, Farkas / Medzihradszky, Katalin F

Glycoconjugate journal

2016 Volume 33, Issue 3, Page(s) 435–445

Abstract: In this work O-linked glycopeptides bearing mucin core-1 type structures were enriched from human serum. Since about 70 % of the O-glycans in human serum bind to the plant lectin Jacalin, we tested a previously successful protocol that combined Jacalin ... ...

Abstract	In this work O-linked glycopeptides bearing mucin core-1 type structures were enriched from human serum. Since about 70 % of the O-glycans in human serum bind to the plant lectin Jacalin, we tested a previously successful protocol that combined Jacalin affinity enrichment on the protein- and peptide-level with ERLIC chromatography as a further enrichment step in between, to eliminate the high background of unmodified peptides. In parallel, we developed a simpler and significantly faster new workflow that used two lectins sequentially: wheat germ agglutinin and then Jacalin. The first lectin provides general glycopeptide enrichment, while the second specifically enriches O-linked glycopeptides with Galβ1-3GalNAcα structures. Mass spectrometric analysis of enriched samples showed that the new sample preparation method is more selective and sensitive than the former. Altogether, 52 unique glycosylation sites in 20 proteins were identified in this study.
Language	English
Publishing date	2016-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	283770-5
ISSN	1573-4986 ; 0282-0080
ISSN (online)	1573-4986
ISSN	0282-0080
DOI	10.1007/s10719-015-9630-6
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Article ; Online: BGP-15 Protects Mitochondria in Acute, Acetaminophen Overdose Induced Liver Injury.

Sarnyai, Farkas / Szekerczés, Timea / Csala, Miklós / Sümegi, Balázs / Szarka, András / Schaff, Zsuzsa / Mandl, József

Pathology oncology research : POR

2019 Volume 26, Issue 3, Page(s) 1797–1803

Abstract: Acetaminophen (APAP) induced hepatotoxicity involves activation of c-Jun amino-terminal kinase (JNK), mitochondrial damage and ER stress. BGP-15, a hydroximic acid derivative, has been reported to have hepatoprotective effects in APAP overdose induced ... ...

Abstract	Acetaminophen (APAP) induced hepatotoxicity involves activation of c-Jun amino-terminal kinase (JNK), mitochondrial damage and ER stress. BGP-15, a hydroximic acid derivative, has been reported to have hepatoprotective effects in APAP overdose induced liver damage. Effect of BGP-15 was further investigated on mitochondria in APAP-overdose induced acute liver injury in mice. We found that BGP-15 efficiently preserved mitochondrial morphology, and it caused a marked decrease in the number of damaged mitochondria. Attenuation of mitochondrial damage by BGP-15 is supported by immunohistochemistry as the TOMM20 label and the co-localized autophagy markers detected in the livers of APAP-treated mice were markedly reduced upon BGP-15 administration. This effect, along with the observed prevention of JNK activation likely contribute to the mitochondrial protective action of BGP-15.
MeSH term(s)	Acetaminophen/toxicity ; Analgesics, Non-Narcotic/toxicity ; Animals ; Chemical and Drug Induced Liver Injury/pathology ; Enzyme Inhibitors/pharmacology ; Liver/drug effects ; Liver/pathology ; Mice ; Mitochondria/drug effects ; Oximes/pharmacology ; Piperidines/pharmacology
Chemical Substances	Analgesics, Non-Narcotic ; Enzyme Inhibitors ; Oximes ; Piperidines ; Acetaminophen (362O9ITL9D) ; BGP 15 (RLN2GTG4YS)
Language	English
Publishing date	2019-11-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1375979-6
ISSN	1532-2807 ; 1219-4956
ISSN (online)	1532-2807
ISSN	1219-4956
DOI	10.1007/s12253-019-00721-1
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Article ; Online: Different Metabolism and Toxicity of TRANS Fatty Acids, Elaidate and Vaccenate Compared to Cis-Oleate in HepG2 Cells.

Sarnyai, Farkas / Kereszturi, Éva / Szirmai, Kitti / Mátyási, Judit / Al-Hag, Johanna Iman / Csizmadia, Tamás / Lőw, Péter / Szelényi, Péter / Tamási, Viola / Tibori, Kinga / Zámbó, Veronika / Tóth, Blanka / Csala, Miklós

International journal of molecular sciences

2022 Volume 23, Issue 13

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 ...

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.
MeSH term(s)	Ceramides/metabolism ; Diglycerides/metabolism ; Fatty Acids/metabolism ; Hep G2 Cells ; Humans ; Oleic Acid/chemistry ; Oleic Acid/toxicity ; Oleic Acids ; Palmitates/toxicity ; Trans Fatty Acids
Chemical Substances	Ceramides ; Diglycerides ; Fatty Acids ; Oleic Acids ; Palmitates ; Trans Fatty Acids ; Oleic Acid (2UMI9U37CP) ; elaidic acid (4837010H8C)
Language	English
Publishing date	2022-06-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23137298
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Article ; Online: Molecular Mechanisms Underlying the Elevated Expression of a Potentially Type 2 Diabetes Mellitus Associated SCD1 Variant.

Tibori, Kinga / Orosz, Gabriella / Zámbó, Veronika / Szelényi, Péter / Sarnyai, Farkas / Tamási, Viola / Rónai, Zsolt / Mátyási, Judit / Tóth, Blanka / Csala, Miklós / Kereszturi, Éva

International journal of molecular sciences

2022 Volume 23, Issue 11

Abstract: Disturbances in lipid metabolism related to excessive food intake and sedentary lifestyle are among major risk of various metabolic disorders. Stearoyl-CoA desaturase-1 (SCD1) has an essential role in these diseases, as it catalyzes the synthesis of ... ...

Abstract	Disturbances in lipid metabolism related to excessive food intake and sedentary lifestyle are among major risk of various metabolic disorders. Stearoyl-CoA desaturase-1 (SCD1) has an essential role in these diseases, as it catalyzes the synthesis of unsaturated fatty acids, both supplying for fat storage and contributing to cellular defense against saturated fatty acid toxicity. Recent studies show that increased activity or over-expression of SCD1 is one of the contributing factors for type 2 diabetes mellitus (T2DM). We aimed to investigate the impact of the common missense rs2234970 (M224L) polymorphism on SCD1 function in transfected cells. We found a higher expression of the minor Leu224 variant, which can be attributed to a combination of mRNA and protein stabilization. The latter was further enhanced by various fatty acids. The increased level of Leu224 variant resulted in an elevated unsaturated: saturated fatty acid ratio, due to higher oleate and palmitoleate contents. Accumulation of Leu224 variant was found in a T2DM patient group, however, the difference was statistically not significant. In conclusion, the minor variant of rs2234970 polymorphism might contribute to the development of obesity-related metabolic disorders, including T2DM, through an increased intracellular level of SCD1.
MeSH term(s)	Diabetes Mellitus, Type 2/genetics ; Fatty Acids/metabolism ; Humans ; Lipid Metabolism/genetics ; Metabolic Diseases ; Stearoyl-CoA Desaturase/genetics ; Stearoyl-CoA Desaturase/metabolism
Chemical Substances	Fatty Acids ; SCD1 protein, human (EC 1.14.19.1) ; Stearoyl-CoA Desaturase (EC 1.14.19.1)
Language	English
Publishing date	2022-06-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23116221
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Article: Investigation of the putative rate‐limiting role of electron transfer in fatty acid desaturation using transfected HEK293T cells

Zámbó, Veronika / Simon‐Szabó, Laura / Sarnyai, Farkas / Mátyási, Judit / Gór‐Nagy, Zsófia / Somogyi, Anna / Szelényi, Péter / Kereszturi, Éva / Tóth, Blanka / Csala, Miklós

FEBS letters. 2020 Feb., v. 594, no. 3

2020

Abstract: 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 ... ...

Abstract	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.
Keywords	electron transfer ; fatty acids ; palmitates ; stearoyl-CoA desaturase ; toxicity
Language	English
Dates of publication	2020-02
Size	p. 530-539.
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	JOURNAL ARTICLE
ZDB-ID	212746-5
ISSN	1873-3468 ; 0014-5793
ISSN (online)	1873-3468
ISSN	0014-5793
DOI	10.1002/1873-3468.13622
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Article ; Online: Microsomal pre-receptor cortisol production is inhibited by resveratrol and epigallocatechin gallate through different mechanisms.

Szelényi, Péter / Somogyi, Anna / Sarnyai, Farkas / Zámbó, Veronika / Simon-Szabó, Laura / Kereszturi, Éva / Csala, Miklós

BioFactors (Oxford, England)

2018 Volume 45, Issue 2, Page(s) 236–243

Abstract: Local activation of cortisol in hormone target tissues is a major determinant of glucocorticoid effect. Disorders in this peripheral cortisol metabolism play an important role in the development of metabolic diseases, such as obesity or type 2 diabetes ... ...

Abstract	Local activation of cortisol in hormone target tissues is a major determinant of glucocorticoid effect. Disorders in this peripheral cortisol metabolism play an important role in the development of metabolic diseases, such as obesity or type 2 diabetes mellitus. Hence, dietary factors influencing the activity of the involved enzymes can have major impacts on the risk of the above diseases. Resveratrol and epigallocatechin gallate (EGCG), two natural polyphenols found in several nutriments and in green tea, respectively, are well-known for their antiobesity and antidiabetic activities. EGCG has been shown to interfere with microsomal cortisol production through decreasing the luminal NADPH:NADP
MeSH term(s)	Animals ; Catechin/analogs & derivatives ; Catechin/pharmacology ; Chromatography, High Pressure Liquid ; Cortisone/metabolism ; Hydrocortisone/metabolism ; Male ; Microsomes, Liver/drug effects ; Microsomes, Liver/metabolism ; Rats ; Resveratrol/pharmacology
Chemical Substances	Catechin (8R1V1STN48) ; epigallocatechin gallate (BQM438CTEL) ; Resveratrol (Q369O8926L) ; Cortisone (V27W9254FZ) ; Hydrocortisone (WI4X0X7BPJ)
Language	English
Publishing date	2018-11-29
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	59230-4
ISSN	1872-8081 ; 0951-6433
ISSN (online)	1872-8081
ISSN	0951-6433
DOI	10.1002/biof.1477
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Article ; Online: Effect of cis- and trans-Monounsaturated Fatty Acids on Palmitate Toxicity and on Palmitate-induced Accumulation of Ceramides and Diglycerides.

Sarnyai, Farkas / Somogyi, Anna / Gór-Nagy, Zsófia / Zámbó, Veronika / Szelényi, Péter / Mátyási, Judit / Simon-Szabó, Laura / Kereszturi, Éva / Tóth, Blanka / Csala, Miklós

International journal of molecular sciences

2020 Volume 21, Issue 7

Abstract: 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- ... ...

Abstract	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.
MeSH term(s)	Animals ; Apoptosis/drug effects ; Cell Line ; Cell Survival/drug effects ; Ceramides/metabolism ; Diglycerides/metabolism ; Dose-Response Relationship, Drug ; Endoplasmic Reticulum Stress/drug effects ; Fatty Acids, Monounsaturated/chemistry ; Fatty Acids, Monounsaturated/pharmacology ; Lipid Metabolism/drug effects ; Palmitates/adverse effects ; Rats
Chemical Substances	Ceramides ; Diglycerides ; Fatty Acids, Monounsaturated ; Palmitates
Language	English
Publishing date	2020-04-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21072626
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