期刊
FRONTIERS IN PHARMACOLOGY
卷 13, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2022.833705
关键词
limonin; AMPK; lipid accumulation; NAFLD; SREBP
资金
- National Natural Science Foundation of China [81903873]
- Natural Science Foundation of Zhejiang Province [LQ19H160002]
- Medical and Health Technology Projects of Zhejiang Province, China [2020PY087, 2019PY089, 2017KY696]
- Chinese medicine science foundation of Zhejiang Province, China [2021ZB328]
- Quzhou technology projects, China [2019K34, 2018K20]
This study reported the inhibitory effect of limonin on hepatic lipid accumulation and fatty acid synthesis in HFD fed mice, and found that this effect was dependent on the activation of AMPK. The activation of AMPK by limonin was achieved by inhibiting cellular energy metabolism and increasing the ADP:ATP ratio, leading to the suppression of the transcriptional activity of SREBP1/2. These findings suggest that limonin may be a promising therapeutic agent for the treatment of NAFLD.
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.
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