SREBP-1c Deficiency Attenuates Fructose-Induced Lipid Droplet Accumulation

Year 2025, Volume: 15 Issue: 1, 210 - 216, 28.03.2025

Seher Mese-tayfur , Ibrahim Isot , Bengu Cetinkaya , Tugce Demirel-yalciner , Nesrin Kartal Ozer , Erdi Sozen

https://doi.org/10.33808/clinexphealthsci.1603452

Abstract

Objective: Sterol regulatory element binding protein 1c (SREBP-1c), a transcription factor involved in the biosynthesis of fatty acids, is critical in metabolic dysfunction-associated fatty liver disease (MAFLD) by promoting lipid accumulation and metabolic dysregulation that leads to hepatic pathologies. Fructose, becoming increasingly common in diets, activates SREBP-1c by increasing acetyl-CoA production. Present study aimed to sought the effect of SREBP-1c in fructose induced lipid accumulation.
Methods: A fructose-induced lipid accumulation model was developed in mouse hepatocyte cells (AML12), where SREBP-1c expression was inhibited through siRNA transfection. Following different fructose concentrations, viability was determined by MTT assay, and the protein expression of SREBP-1c protein was determined by western blotting. The number of lipid droplets (LDs) was quantified microscopically, and lipogenic mRNA expressions of FASN, SCD1, GPAM, ACLY, ACSL1 and ACACA were detected by qRT-PCR.
Results: Western blotting and microscopic analysis indicated that 25 mM for 72 hours of fructose increased total LDs, together with SREBP-1c levels, without affecting cell viability. The mRNA expression of SREBP-1c decreased in the presence of siRNA, confirming siRNA efficacy. SREBP-1c silencing reduced the number of fructose-induced total LDs. As lipogenic mRNA expressions, SREBP-1c silencing reduced SCD1 and ACLY, while other genes were unaffected.
Conclusion: Silencing of SREBP-1c in hepatocytes demonstrated its beneficial effect by reducing fructose-induced LD accumulation.

Keywords

Sterol regulatory element binding transcription factor 1c, Fructose, Lipid accumulation

Ethical Statement

This study was approved by Ethics Committee of Marmara University, School of Medicine Ethics Committee (Approval date: 01.02.2019; Number: 09.2019.188).

Supporting Institution

The Scientific and Technological Research Council of Turkey (TUBITAK).

Project Number

This work was supported by the The Scientific and Technological Research Council of Turkey (TUBITAK) [grant number 323S171].

Thanks

We would like to thank Marmara University for providing access to academic databases.

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