2. Academic Validation
  3. Sesamin alleviates lipid accumulation induced by oleic acid via PINK1/Parkin-mediated mitophagy in HepG2 cells

Sesamin alleviates lipid accumulation induced by oleic acid via PINK1/Parkin-mediated mitophagy in HepG2 cells

  • Biochem Biophys Res Commun. 2024 May 14:708:149815. doi: 10.1016/j.bbrc.2024.149815.
Mengyun Dong 1,  Tianliang Zhang 2,  Xueli Liang 1,  Xinyi Cheng 1,  Fuyan Shi 1,  Hang Yuan 1,  Fengxiang Zhang 1,  Qiqi Jiang 3,  Xia Wang 4
Affiliations

Affiliations

  • 1 School of Public Health, Shandong Second Medical University, Weifang, Shandong, 261053, China.
  • 2 Experimental Center for Medical Research, Shandong Second Medical University, Weifang, Shandong, 261053, China.
  • 3 Department of Gastroenterology, Weifang People's Hospital, Shandong Second Medical University, Weifang, Shandong, 261000, China. Electronic address: [email protected].
  • 4 Department of Gastroenterology, Weifang People's Hospital, Shandong Second Medical University, Weifang, Shandong, 261000, China. Electronic address: [email protected].
PMID: 38531220 DOI: 10.1016/j.bbrc.2024.149815
Abstract

Sesamin, a special compound present in sesame and sesame oil, has been reported a role in regulating lipid metabolism, while the underlying mechanisms remain unclear. Autophagy has been reported associated with lipid metabolism and regarded as a key modulator in liver steatosis. The present work aimed to investigate whether sesamin could exert its protective effects against lipid accumulation via modulating Autophagy in HepG2 cells stimulated with oleic acid (OA). Cell viability was evaluated using the CCK-8 method, and triglycerides (TG), total Cholesterol (TC), high-density lipoprotein Cholesterol (HDL-C), low-density lipoprotein, Cholesterol (LDL-C), alanine aminotransferase (ALT), along with aspartate aminotransferase (AST) were assessed by oil red O staining, transmission electron microscopy (TEM), and biochemical kits to investigate the lipid-lowering effects of sesamin. Differentially expressed genes were screened by RNA Sequencing and validated using real-time quantitative PCR and Western blot. Autophagy and Mitophagy related molecules were analyzed employing TEM, Western blot, and immunofluorescence. The data shows that in HepG2 cells stimulated by OA, sesamin reduces levels of TG, TC, LDL-C, ALT, and AST while elevating HDL-C, alleviates the lipid accumulation and improves fatty acid metabolism through modulating the levels of fat metabolism related genes including PCSK9, FABP1, CD36, and SOX4. Sesamin restores the suppressed Autophagy in HepG2 cells caused by OA, which could be blocked by Autophagy inhibitors. This indicates that sesamin improves fatty acid metabolism by enhancing Autophagy levels, thereby mitigating the intracellular lipid accumulation. Furthermore, sesamin significantly enhances the Mitophagy and improves mitochondrial homeostasis via activating the PINK/Parkin pathway. These data suggest that sesamin alleviates the excessive lipid accumulation in HepG2 caused by OA by restoring the impaired Mitophagy via the PINK1/Parkin pathway, probably playing a preventive or therapeutic role in hepatic steatosis.

Keywords

Autophagy; HepG2; Lipid accumulation; Lipid metabolism; Mitophagy; Sesamin.

Figures
Products