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Published on: February 3, 2017
Cherry Anthocyanins Regulate NAFLD by Promoting Autophagy Pathway
Qiang Chu1,2,3, Shuang Zhang4, Meng Chen1,2,3
1Department of Food Science and Nutrition, Zhejiang University, Hangzhou 310058, China.
Abstract:
Nonalcoholic fatty liver disease (NAFLD) is a common chronic disease that threatens human health, and present therapies remain limited due to the lack of effective drugs. Lipid metabolic disturbance and oxidative stress have strong links to the development of NAFLD, while autophagy was generally accepted as a key regulatory mechanism on these steps. Our previous studies indicated that cherry anthocyanins (CACN) protected against high fat diet-induced obesity and NALFD in C57BL/6 mice, while the underlying molecule mechanism is still unclear. Thus, in this study, we show that CACN protect against oleic acid- (OA-) induced oxidative stress and attenuate lipid droplet accumulation in NAFLD cell models. According to the results of a transmission electron microscope (TEM), western blot, immunofluorescence (IF), and adenovirus transfection (Ad-mCherry-GFP-LC3B), autophagy is in accordance with the lipid-lowering effect induced by CACN. Further studies illustrate that CACN may activate autophagy via mTOR pathways. In addition, an autophagy inhibitor, 3-methyladenine (3-MA), was applied and the result suggested that autophagy indeed participates in the lipid clearance process in OA-induced lipid accumulation. All these results indicate that the positive effects of CACN on OA-induced hepatic lipid accumulation are mediated via activating autophagy, showing a potential target for the therapeutic strategy of NAFLD.
Insights
Cherry anthocyanins (CACN) combat nonalcoholic fatty liver disease (NAFLD) by reducing liver fat accumulation and oxidative stress. These compounds activate autophagy, a cellular process crucial for clearing excess lipids, offering a potential therapeutic avenue for NAFLD.
Area of Science:
- Biochemistry
- Cell Biology
- Hepatology
Background:
- Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic condition with limited therapeutic options.
- Lipid metabolism dysfunction and oxidative stress are key contributors to NAFLD pathogenesis.
- Autophagy plays a critical role in regulating these cellular processes.
Purpose of the Study:
- To investigate the protective effects of cherry anthocyanins (CACN) against oleic acid-induced NAFLD cell models.
- To elucidate the molecular mechanisms underlying CACN's therapeutic potential in NAFLD.
- To determine the role of autophagy in CACN-mediated lipid clearance.
Main Methods:
- Utilized oleic acid (OA)-induced NAFLD cell models.
- Employed transmission electron microscopy (TEM), western blot, and immunofluorescence (IF) for cellular analysis.
- Investigated autophagy activation using Ad-mCherry-GFP-LC3B and an autophagy inhibitor (3-methyladenine).
Main Results:
- CACN demonstrated protective effects against OA-induced oxidative stress and lipid droplet accumulation.
- Autophagy activation was observed to correlate with the lipid-lowering effects of CACN.
- CACN were found to activate autophagy potentially through the mTOR pathway.
- Inhibition of autophagy abrogated the beneficial effects of CACN on lipid accumulation.
Conclusions:
- Cherry anthocyanins (CACN) effectively mitigate hepatic lipid accumulation and oxidative stress in NAFLD models.
- CACN exert their therapeutic effects by activating autophagy, likely via the mTOR pathway.
- Autophagy is essential for the lipid-clearing action of CACN, highlighting it as a promising therapeutic target for NAFLD.
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