Related Experiment Video
Updated: Jan 14, 2026
Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
PLIN5 deficiency ameliorates metabolic dysfunction‑associated fatty liver disease by inhibiting ferroptosis
Ya Li1, Xiaohan Wang2, Xuecui Yin3
1Henan Joint International Research Laboratory of Chronic Liver Injury and Henan Provincial Outstanding Overseas Scientists Chronic Liver Injury Workshop, Henan Key Laboratory of Rehabilitation Medicine, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China.
Abstract:
Metabolic‑associated fatty liver disease (MAFLD) is widely recognized as the most common type of chronic liver disease. As a member of the perilipin (PLIN) family, PLIN5 serves an important role in the regulation of lipid metabolism. Ferroptosis is a form of iron‑dependent non‑apoptotic cell death characterized by lipid peroxidation. Notably, knockout of PLIN5 can attenuate high‑fat diet (HFD)‑induced MAFLD; however, the specific underlying mechanism remains unclear. The present study induced PLIN5 overexpression by transfecting AML12 cells with a pcDNA3.1‑PLIN5 plasmid, and PLIN5 knockdown was achieved using short hairpin RNA‑mediated interference. Subsequently, intracellular ferrous iron (Fe2+) levels were assessed via immunofluorescence staining. Furthermore, a MAFLD model was established in C57BL/6J mice by feeding them a HFD. To establish an in vitro model of hepatic steatosis, AML12 hepatocytes were treated with palmitic acid and oleic acid to induce intracellular lipid accumulation. To further explore the effects of PLIN5 on ferroptosis, liver single‑cell sequencing was conducted and cellular experiments were performed to assess changes in redox and ferroptosis‑related proteins. The current study investigated the effects of PLIN5 on MAFLD in animal and cellular experiments, including the changes in lipid accumulation, redox and ferroptosis‑related markers. The results revealed that genetic knockdown of PLIN5 significantly attenuated lipid accumulation and intracellular Fe2+ levels in AML12 hepatocytes, whereas PLIN5 overexpression markedly exacerbated these parameters. In addition, PLIN5 deficiency substantially reduced malondialdehyde content while enhancing glutathione levels, indicating attenuated oxidative stress. The results of the in vivo studies demonstrated that PLIN5 knockout effectively ameliorated MAFLD progression in mice by suppressing ferroptosis. In conclusion, PLIN5 knockout may delay the progression of MAFLD in mice via ferroptosis inhibition. Therefore, targeting PLIN5 could offer a novel therapeutic strategy to address MAFLD by modulating lipid metabolism and ferroptosis pathways.
Insights
Genetic knockdown of PLIN5 reduces lipid accumulation and ferroptosis in metabolic-associated fatty liver disease (MAFLD). PLIN5 knockout ameliorates MAFLD progression by inhibiting ferroptosis, suggesting PLIN5 as a therapeutic target.
Area of Science:
- Hepatology
- Cell Biology
- Biochemistry
Background:
- Metabolic-associated fatty liver disease (MAFLD) is the most common chronic liver disease.
- PLIN5 regulates lipid metabolism and is implicated in MAFLD.
- Ferroptosis, an iron-dependent cell death, is linked to MAFLD pathogenesis.
Purpose of the Study:
- To investigate the role of PLIN5 in MAFLD.
- To elucidate the underlying mechanisms by which PLIN5 influences lipid metabolism and ferroptosis in MAFLD.
- To evaluate PLIN5 as a potential therapeutic target for MAFLD.
Main Methods:
- MAFLD models were established in C57BL/6J mice fed a high-fat diet (HFD) and in AML12 hepatocytes treated with fatty acids.
- PLIN5 expression was manipulated using pcDNA3.1-PLIN5 plasmid for overexpression and short hairpin RNA for knockdown.
- Intracellular ferrous iron, lipid accumulation, redox status, and ferroptosis-related proteins were assessed.
- Liver single-cell sequencing was performed.
Main Results:
- PLIN5 knockdown attenuated lipid accumulation and intracellular ferrous iron levels in hepatocytes.
- PLIN5 overexpression exacerbated lipid accumulation and ferrous iron levels.
- PLIN5 deficiency reduced malondialdehyde and increased glutathione, indicating reduced oxidative stress.
- PLIN5 knockout ameliorated MAFLD progression in mice by suppressing ferroptosis.
Conclusions:
- PLIN5 plays a significant role in MAFLD progression by modulating lipid metabolism and promoting ferroptosis.
- PLIN5 knockout delays MAFLD progression by inhibiting ferroptosis.
- Targeting PLIN5 offers a potential therapeutic strategy for MAFLD.
More Related Videos
08:20Investigating the Protective Effects of Platycodin D on Non-Alcoholic Fatty Liver Disease in a Palmitic Acid-Induced In Vitro Model
Published on: December 2, 2022
07:03Author Spotlight: Establishing MASLD Cell Models for Investigating Disease Mechanisms and the Lipid-Lowering Effects of Koumiss
Published on: July 19, 2024
