Journal article
Quercetin ameliorates nonalcoholic fatty liver disease (NAFLD) via the promotion of AMPK-mediated hepatic mitophagy
The Journal of Nutritional Biochemistry, Vol.120, pp.1-11
2023
PMID: 37423322
Abstract
The global incidence of nonalcoholic fatty liver disease (NAFLD) has been surging in recent years, however, no drug is currently approved to treat this disease. Quercetin, a natural flavonoid abundant in plants and fruits, has been reported to alleviate NAFLD, however, the exact molecular mechanism remains unclear. This study aims to further elucidate its potential mechanism of action. The beneficial effects and the underlying mechanism of quercetin in alleviating NAFLD were explored both in vitro and in vivo, by employing chemical inhibitors of autophagosomes (3-methyladenine, 3-MA), autolysosomes (chloroquine, CQ), AMPK (Compound C, CC) and SIRT1 (selisistat, EX-527). The levels of intracellular lipids, reactive oxygen species, mitochondria function, autophagy, and mitophagy were assessed by fluorescent labeling and examined using flow cytometry or confocal microscopy. Key protein expressions of autophagy, mitophagy, and inflammation were also determined. In vivo, quercetin was shown to dose-dependently effectively alleviate NAFLD, but intraperitoneal injection of 3-MA could block the beneficial effects of quercetin on body weight, liver weight, serum ALT/AST, hepatic ROS and inflammation. In vitro, quercetin could reduce intracellular lipids (Nile Red staining) and ROS/DHE accumulation, which could be also blocked by 3-MA or CQ. Furthermore, we found that CC could abrogate the protective effects of quercetin on lipid and ROS accumulation in vitro. Also, CC abolished the proautophagic and anti-inflammatory effects of quercetin, as shown by western blot determination and Lyso-Tracker labeling. Importantly, mitophagy, a specific form of mitochondria-targeted autophagy, was enhanced by quercetin, as demonstrated by PINK1/Parkin protein variation and immunofluorescence colocalization of autophagosomes and mitochondria, which could also be blocked by the intervention of CC. This study demonstrates that quercetin prevents NAFLD through AMPK-mediated mitophagy and suggests that promoting mitophagy via an upregulation of AMPK may be a promising therapeutic strategy against NAFLD.
Details
- Title
- Quercetin ameliorates nonalcoholic fatty liver disease (NAFLD) via the promotion of AMPK-mediated hepatic mitophagy
- Authors
- Peng Cao (Corresponding Author) - Huazhong University of Science and TechnologyYi Wang - Sichuan Academy of Medical Sciences & Sichuan Provincial People's HospitalCong Zhang - Hubei University of Chinese MedicineMitchell A Sullivan - University of QueenslandWen Chen - Huazhong University of Science and TechnologyXiang Jing - Guangdong Medical CollegeHuifan Yu - Hubei University of MedicineFei Li - Hubei University of MedicineQu Wang - Guangdong Medical CollegeZhongshi Zhou - Hubei University of Chinese MedicineQi Wang - Hubei University of Chinese MedicineWen Tian - Guangdong Medical CollegeZhenpeng Qiu (Corresponding Author) - Hubei University of Chinese MedicineLianxiang Luo (Corresponding Author) - Guangdong Medical College
- Publication details
- The Journal of Nutritional Biochemistry, Vol.120, pp.1-11
- Publisher
- Elsevier Inc.
- Date published
- 2023
- DOI
- 10.1016/j.jnutbio.2023.109414
- ISSN
- 1873-4847
- PMID
- 37423322
- Organisation Unit
- School of Health - Biomedicine
- Language
- English
- Record Identifier
- 991035093002621
- Output Type
- Journal article
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- Domestic collaboration
- International collaboration
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- Biochemistry & Molecular Biology
- Nutrition & Dietetics
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