Deficiency of SREBP1c modulates autophagy mediated lipid droplet catabolism during oleic acid induced steatosis

Erdi Sozen; Tugce Demirel-Yalciner; Dyana Sari; Ceren Avcilar; Tuna Felix Samanci; Nesrin Kartal Ozer

doi:10.1016/j.metop.2021.100138

Deficiency of SREBP1c modulates autophagy mediated lipid droplet catabolism during oleic acid induced steatosis

Metabol Open. 2021 Oct 13:12:100138. doi: 10.1016/j.metop.2021.100138. eCollection 2021 Dec.

Authors

Erdi Sozen^{1

2}, Tugce Demirel-Yalciner¹, Dyana Sari¹, Ceren Avcilar¹, Tuna Felix Samanci¹, Nesrin Kartal Ozer¹

Affiliations

¹ Department of Biochemistry, Faculty of Medicine, Marmara University, Maltepe, Istanbul, 34854, Turkey.
² Genetic and Metabolic Diseases Research and Investigation Center (GEMHAM), Marmara University, Maltepe, Istanbul, 34854, Turkey.

Abstract

Objective: Increased fatty acid and triglyceride synthesis in liver, majorly modulated by Sterol Regulator Elementing Binding Protein 1c (SREBP1c), is one of the main features of non-alcoholic fatty liver disease (NAFLD). In the present study, we aimed to identify the relation between SREBP1c and autophagy mediated lipid droplet (LD) catabolism in oleic acid (OA) induced lipid accumulation.

Methods: Increased LD formation and SREBP1c induction were identified in hepatocytes (AML12 cells) following the OA administration. SREBP1c level was reduced through siRNA against SREBP1c. The amount and the size of LDs were determined by BODIPY, while protein and mRNA expressions were identified by immunoblotting and qRT-PCR, respectively. LD-lysosome colocalization was determined with immunofluorescence.

Results: Increased LD formation and SREBP1c levels were determined at 0.06 mM OA concentration. SREBP1c silencing reduced the number of LDs, while increasing mRNA levels of PPARα. On the other hand, SREBP1c silencing in non-OA and OA treated cells enhanced autophagy mediated LD catabolism.

Conclusion: Our results implicate the effect of SREBP1c deficiency in modulating PPARα signaling and autophagy mediated LD catabolism against OA induced lipid accumulation.

Keywords: Autophagy; FASN, Fatty acid synthase; LAMP1, Lysosomal-associated membrane protein 1; LC3, Microtubule-Associated Protein Light Chain 3; LD, Lipid droplet; Lipid accumulation; NAFLD, Nonalcoholic fatty liver disease; Non-alcoholic fatty liver disease; OA, Oleic acid; PA, Palmitic acid; PPARα, Peroxisome proliferator activated receptor alpha; SCD-1, Stereoyl-CoA desaturase-1; SREBP, Sterol regulatory element binding protein; SREBP1c.