PhD Scientific Days 2023

Molecular Sciences II.

ETS1- and trans fatty acid-dependent regulation of SCD1 expression modified by the promoter polymorphism rs1054411

Előadó neve

Tibori, Kinga

Neptun code

CBS1VP

Előadó munkahelye

Semmelweis University, Department of Molecular Biology

Előadó telefonszáma

06302348363

Előadó e-mail címe

kinga.egyetemi@gmail.com

Az előadás címe

ETS1- and trans fatty acid-dependent regulation of SCD1 expression modified by the promoter polymorphism rs1054411

Szerző(k) neve és munkahelye

Kinga Tibori 1, Veronika Zámbó 1, Miklós Csala 1, Éva Kereszturi 1
1 Department of Molecular Biology, Semmelweis University, Budapest, Hungary

Bemutatás módja

Szóbeli

Szekció

Molecular Sciences II.

Language of the presentation

Hungarian

Preferred session

Molecular Sciences

Összefoglaló szövege

Introduction: Syndromes associated with excessive food intake and sedentary lifestyle may be due to systemic disturbances in lipid metabolism. A crucial enzyme in the defense against lipotoxicity is the Stearoyl-CoA desaturase-1 (SCD1), catalyzing the unsaturated fatty acid synthesis. On the other hand, increased activity or overexpression of the enzyme is a potential risk factor for type II diabetes mellitus (T2DM) as it favors fat storage and obesity.
Aims: In this study we sought to investigate the influence of different types of fatty acids (FAs), including saturated and monounsaturated cis or trans fatty acids, on the expression of SCD1 containing the most common promoter polymorphisms. On the other hand, we examined whether these polymorphisms affect any transcription factor (TF) binding sites of the promoter region.
Methods: Impact of FAs on the endogenous and transiently transfected SCD1 in HEK293T and HepG2 cells was monitored by immunoblotting and qPCR. Four promoter variants were generated by site-directed mutagenesis. The effect of SCD1 promoter polymorphisms on the TF binding site was investigated in silico with the JASPAR program and in vitro with a luciferase reporter system.
Results: We demonstrated that both the protein and mRNA level of the SCD1 significantly increases in response to elaidate (18:1 trans Δ9) compared to vaccinate (18:1 trans Δ11). This effect was also confirmed in the luciferase reporter system. The four most common promoter polymorphisms alone did not affect the promoter activity of SCD1, however, rs1054411 enhanced it in the presence of FAs, especially in the case of the two trans FA, elaidate and vacccenate. Based on our in silico analysis, in the presence of the minor allele of this polymorphism, the probability of ETS1 TF binding to the SCD1 promoter is reduced by 20%. Co-transfection with SCD1 promoter constructions with different alleles and ETS1 expression vector confirmed the reduced affinity of ETS1 to rs1054411_G variant.
Conclusions: From our results we conclude that the rs1054411 polymorphism may influence the protective role of SCD1 by modifying its promoter sensitivity to different fatty acids and altering its expression through the reduction of ETS1 promoter binding affinity.
Funding: This work was supported by the Hungarian National Research, Development and Innovation Office (NKFIH grant number: FK138115).

University and Doctoral School

Semmelweis University, Doctoral School of Molecular Medicine

Supervisor

Éva Kereszturi, Miklós Csala

Publication of my abstract

I give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

6874

Start

15:15

End

15:30

Authors (legacy)

Kinga Tibori 1, Veronika Zámbó 1, Miklós Csala 1, Éva Kereszturi 1
1 Department of Molecular Biology, Semmelweis University, Budapest, Hungary