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Published on: March 11, 2017
Rhein alleviates hepatic steatosis in NAFLD mice by activating the AMPK/ACC/SREBP1 pathway to enhance lipid
Weiwei Dai1, Qishu Hou1, Jifeng Ye2
1Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, No. 109 West Road, Lucheng District, Wenzhou, 325000, Zhejiang, China.
Background:
Non-alcoholic fatty liver disease (NAFLD) is a common metabolic liver disorder characterized by excessive lipid accumulation. The 5'-adenosine monophosphate-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC)/sterol regulatory element-binding protein 1 (SREBP1) pathway plays a pivotal role in regulating lipid metabolism. Rhein, a natural compound, has demonstrated hepatoprotective potential; however, its mechanism of action in NAFLD remains unclear. This study aimed to investigate whether rhein ameliorates NAFLD through modulation of the AMPK/ACC/SREBP1 pathway.
Methods:
A murine NAFLD model was established using a high-fat diet (HFD). Mice were treated with varying doses of rhein, and their body weight, liver, kidney, and retroperitoneal fat weights were recorded. Liver pathology was assessed by histological examination and Oil Red O staining. Serum lipid profiles, liver function biomarkers, and inflammatory cytokine levels were measured. Western blotting was employed to analyze the expression and phosphorylation of AMPK pathway-related proteins (AMPK, ACC, and SREBP1). To validate the involvement of this pathway, AMPK-IN-3 was intraperitoneally administered in combination with high-dose rhein to a subset of HFD-fed mice.
Results:
Rhein treatment significantly reduced body weight gain, organ weights, hepatic lipid accumulation, serum cholesterol and triglyceride levels, and the expression of inflammatory cytokines in NAFLD mice. It also improved liver function markers, enhanced AMPK phosphorylation, promoted ACC phosphorylation, and inhibited SREBP1 expression. Notably, co-treatment with AMPK-IN-3 attenuated these beneficial effects, confirming the mechanistic involvement of the AMPK/ACC/SREBP1 pathway.
Conclusion:
Rhein confers protective effects against HFD-induced NAFLD by activating the AMPK/ACC/SREBP1 signaling pathway, thereby enhancing hepatic lipid metabolism, reducing steatosis, and alleviating liver injury and inflammation. These findings suggest that rhein may serve as a promising therapeutic candidate for NAFLD.
Insights
Rhein, a natural compound, effectively treats non-alcoholic fatty liver disease (NAFLD) by activating the AMPK/ACC/SREBP1 pathway. This natural compound reduces liver fat accumulation and inflammation, offering a promising therapeutic option for NAFLD.
Area of Science:
- Metabolic disorders
- Hepatology
- Pharmacology
Background:
- Non-alcoholic fatty liver disease (NAFLD) is a prevalent metabolic disorder marked by excessive liver lipid accumulation.
- The 5'-adenosine monophosphate-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC)/sterol regulatory element-binding protein 1 (SREBP1) pathway is crucial for regulating lipid metabolism.
- Rhein, a natural compound, shows hepatoprotective potential, but its mechanism in NAFLD requires elucidation.
Purpose of the Study:
- To investigate rhein's efficacy in ameliorating high-fat diet-induced NAFLD in mice.
- To determine if rhein modulates the AMPK/ACC/SREBP1 signaling pathway in NAFLD treatment.
Main Methods:
- Established a murine model of NAFLD using a high-fat diet (HFD).
- Administered varying doses of rhein and assessed physiological and biochemical parameters, including body weight, organ weights, liver pathology, serum lipids, and inflammatory markers.
- Utilized Western blotting to analyze protein expression and phosphorylation within the AMPK/ACC/SREBP1 pathway.
- Validated pathway involvement using AMPK-IN-3 co-treatment.
Main Results:
- Rhein treatment significantly reduced body weight gain, hepatic lipid accumulation, and serum lipid levels.
- Histological and biochemical analyses showed improved liver function and reduced inflammation.
- Rhein enhanced AMPK and ACC phosphorylation while inhibiting SREBP1 expression.
- Co-administration with AMPK-IN-3 diminished rhein's protective effects, confirming pathway mediation.
Conclusions:
- Rhein demonstrates significant protective effects against HFD-induced NAFLD.
- Activation of the AMPK/ACC/SREBP1 pathway by rhein enhances hepatic lipid metabolism and reduces steatosis.
- Rhein alleviates liver injury and inflammation, positioning it as a potential therapeutic candidate for NAFLD.
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