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Microcystin-RR promote lipid accumulation through CD36 mediated signal pathway and fatty acid uptake in HepG2 cells
Wenjuan Jia1, Lin Zhong1, Qingmiao Ren2
1School of Basic Medical Sciences, Qingdao University, Qingdao, 266071, China; Department of Cardiology, Yantai Yuhuangding Hospital, Qingdao University, Yantai, 264000, China.
Abstract:
Microcystins (MC)-RR is a significant analogue of MC-LR, which has been identified as a hepatotoxin capable of influencing lipid metabolism and promoting the progression of liver-related metabolic diseases. However, the toxicity and biological function of MC-RR are still not well understood. In this study, the toxic effects and its role in lipid metabolism of MC-RR were investigated in hepatoblastoma cells (HepG2cells). The results demonstrated that MC-RR dose-dependently reduced cell viability and induced apoptosis. Additionally, even at low concentrations, MC-RR promoted lipid accumulation through up-regulating levels of triglyceride, total cholesterol, phosphatidylcholines and phosphatidylethaolamine in HepG2 cells, with no impact on cell viability. Proteomics and transcriptomics analysis further revealed significant alterations in the protein and gene expression profiles in HepG2 cells treated with MC-RR. Bioinformatic analysis, along with subsequent validation, indicated the upregulation of CD36 and activation of the AMPK and PI3K/AKT/mTOR in response to MC-RR exposure. Finally, knockdown of CD36 markedly ameliorated MC-RR-induced lipid accumulation in HepG2 cells. These findings collectively suggest that MC-RR promotes lipid accumulation in HepG2 cells through CD36-mediated signal pathway and fatty acid uptake. Our findings provide new insights into the hepatotoxic mechanism of MC-RR.
Insights
Microcystin-RR (MC-RR) causes liver cell damage and promotes lipid accumulation by upregulating CD36. This study reveals MC-RR
Area of Science:
- Hepatotoxicity and Lipid Metabolism Research
- Molecular Toxicology
- Cellular Biology
Background:
- Microcystins (MC) are potent hepatotoxins, with MC-LR well-studied.
- The toxicity and specific biological functions of MC-RR remain poorly understood.
- Investigating MC-RR's impact on liver health and lipid metabolism is crucial.
Purpose of the Study:
- To investigate the toxic effects of MC-RR on hepatoblastoma cells (HepG2).
- To elucidate MC-RR's role in regulating lipid metabolism within liver cells.
- To identify the molecular mechanisms underlying MC-RR-induced hepatotoxicity.
Main Methods:
- Exposure of HepG2 cells to varying concentrations of MC-RR.
- Assessment of cell viability, apoptosis, and lipid accumulation (triglyceride, cholesterol).
- Proteomics, transcriptomics, bioinformatic analysis, and gene knockdown (CD36).
Main Results:
- MC-RR reduced HepG2 cell viability and induced apoptosis in a dose-dependent manner.
- Low concentrations of MC-RR promoted significant lipid accumulation, increasing triglyceride and cholesterol levels.
- MC-RR upregulated CD36 expression and activated AMPK and PI3K/AKT/mTOR pathways, with CD36 knockdown mitigating lipid accumulation.
Conclusions:
- MC-RR exerts dose-dependent toxicity and induces apoptosis in HepG2 cells.
- MC-RR promotes lipid accumulation through CD36-mediated signaling and enhanced fatty acid uptake.
- This study provides novel insights into the hepatotoxic mechanisms of MC-RR, highlighting its role in metabolic disruption.
