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

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.