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Updated: Oct 4, 2025
Author Spotlight: Exploring the Relationship Between Lipotoxicity and HFpEF
Published on: March 29, 2024
Limonin, an AMPK Activator, Inhibits Hepatic Lipid Accumulation in High Fat Diet Fed Mice
Si-Wei Wang1, Tian Lan1, Hang-Fei Chen2
1Core Facility, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, China.
Abstract:
NAFLD is the most prevalent liver disease in human history. The treatment is still limited yet. In the current study, we reported that limonin inhibited hepatic lipid accumulation and fatty acid synthesis in HFD fed mice. Using AMPK inhibitor and AMPK deficient C. elegans, we revealed the effect was dependent on the activation of AMPK. We found that limonin activated AMPK through inhibition of cellular energy metabolism and increasing ADP:ATP ratio. Furthermore, the treatment of limonin induced AMPK mediated suppression of the transcriptional activity of SREBP1/2. Our study suggests that limonin may a promising therapeutic agent for the treatment of NAFLD.
Insights
Limonin, a natural compound, effectively reduces liver fat accumulation and synthesis in mice with non-alcoholic fatty liver disease (NAFLD). This therapeutic effect is achieved by activating AMP-activated protein kinase (AMPK).
Area of Science:
- Biochemistry
- Metabolic Diseases
- Pharmacology
Background:
- Non-alcoholic fatty liver disease (NAFLD) is a widespread liver condition with limited therapeutic options.
- Hepatic lipid accumulation and aberrant fatty acid synthesis are key pathological features of NAFLD.
Purpose of the Study:
- To investigate the potential of limonin as a therapeutic agent for NAFLD.
- To elucidate the underlying molecular mechanisms of limonin's action, particularly its effect on AMPK signaling.
Main Methods:
- High-fat diet (HFD) induced NAFLD mouse model.
- Pharmacological inhibition and genetic deficiency of AMP-activated protein kinase (AMPK) in C. elegans.
- Assessment of hepatic lipid content and fatty acid synthesis.
- Measurement of cellular energy metabolism (ADP:ATP ratio).
- Analysis of SREBP1/2 transcriptional activity.
Main Results:
- Limonin treatment significantly inhibited hepatic lipid accumulation and fatty acid synthesis in HFD-fed mice.
- The observed effects of limonin were dependent on AMPK activation, confirmed using AMPK inhibitors and deficient C. elegans.
- Limonin activated AMPK by inhibiting cellular energy metabolism and increasing the ADP:ATP ratio.
- Limonin treatment led to AMPK-mediated suppression of SREBP1/2 transcriptional activity.
Conclusions:
- Limonin demonstrates potential as a therapeutic agent for NAFLD by modulating lipid metabolism.
- The mechanism involves AMPK activation, leading to the suppression of key lipogenic transcription factors.
- Further research into limonin for NAFLD treatment is warranted.
