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Published on: May 26, 2023
Capsaicin regulated lipid metabolism in HepG2 via mitochondrial autophagy PINK1/Parkin pathway
Hao Song1, Minhao Xie2, Hui Xu1
1Collaborative Innovation Center for Modern Grain Circulation and Safety, and College of Food Science and Engineering, Nanjing University of Finance and Economics, Nanjing 210023, China.
Abstract:
Capsaicin (CAP), a major natural functional component in chili peppers, has garnered considerable attention for its health benefits, including lipid-lowering effects, and its precise mechanisms remain unclear. This study aims to investigate the lipid-reducing effects of CAP on oleic acid (OA)-induced lipid accumulation in HepG2 cells and explore the underlying mechanisms. The results showed that CAP exerted lipid-lowering effects by reducing triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and increasing high-density lipoprotein cholesterol (HDL-C) in OA-induced HepG2 cells. CAP modulated the relative expression levels of lipid metabolism-related genes, including ACC, PPAR-α, PPAR-γ, Fasn, CPT-1, SREBP-1C, and SCD-1 in HepG2 cells. Notably, CAP activated the PINK1/Parkin-mediated mitophagy pathway to alleviatie lipid accumulation. Treatment with the mitophagy inhibitor Mdivi-1 reversed the lipid-lowering effect of CAP, and silencing PINK1 gene using siRNA abolished lipid-lowering effect of CAP in HepG2 cells, confirming the critical involvement of the pathway. In conclusion, CAP targeted the PINK1 gene and activated the PINK1/Parkin signaling pathway to promote mitophagy, restoring cellular energy homeostasis and regulating lipid synthesis and degradation, ultimately reducing lipid accumulation. These findings provided a mechanistic basis for the potential use of CAP in developing novel natural therapies for lipid metabolic disorders and obesity management.
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