PUBLICATION
Exercise Intervention Mitigates Pathological Liver Changes in NAFLD Zebrafish by Activating SIRT1/AMPK/NRF2 Signaling
- Authors
- Zou, Y., Chen, Z., Sun, C., Yang, D., Zhou, Z., Peng, X., Zheng, L., Tang, C.
- ID
- ZDB-PUB-211025-38
- Date
- 2021
- Source
- International Journal of Molecular Sciences 22(20): (Journal)
- Registered Authors
- Keywords
- NAFLD, ROS, SIRT1/AMPK/NRF2, exercise, zebrafish
- MeSH Terms
-
- Interleukin-1beta/metabolism
- Zebrafish/metabolism
- Reactive Oxygen Species/metabolism
- Sirtuin 1/metabolism*
- Disease Models, Animal
- Male
- NADPH Oxidase 4/metabolism
- Liver/metabolism
- Liver/pathology*
- Oxidative Stress
- NF-E2-Related Factor 2/metabolism*
- Diet, High-Fat
- Malondialdehyde/metabolism
- Zebrafish Proteins/metabolism
- AMP-Activated Protein Kinases/metabolism*
- Animals
- Physical Conditioning, Animal
- Non-alcoholic Fatty Liver Disease/metabolism
- Non-alcoholic Fatty Liver Disease/pathology
- Antioxidants
- Female
- Signal Transduction*
- PubMed
- 34681600 Full text @ Int. J. Mol. Sci.
Citation
Zou, Y., Chen, Z., Sun, C., Yang, D., Zhou, Z., Peng, X., Zheng, L., Tang, C. (2021) Exercise Intervention Mitigates Pathological Liver Changes in NAFLD Zebrafish by Activating SIRT1/AMPK/NRF2 Signaling. International Journal of Molecular Sciences. 22(20):.
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a common disease that causes serious liver damage. Exercise is recognized as a non-pharmacological tool to improve the pathology of NAFLD. However, the antioxidative effects and mechanisms by which exercise ameliorates NAFLD remain unclear. The present study conducted exercise training on zebrafish during a 12-week high-fat feeding period to study the antioxidant effect of exercise on the liver. We found that swimming exercise decreased lipid accumulation and improved pathological changes in the liver of high-fat diet-fed zebrafish. Moreover, swimming alleviated NOX4-derived reactive oxygen species (ROS) overproduction and reduced methanedicarboxylic aldehyde (MDA) levels. We also examined the anti-apoptotic effects of swimming and found that it increased the expression of antiapoptotic factor bcl2 and decreased the expression of genes associated with apoptosis (caspase3, bax). Mechanistically, swimming intervention activated SIRT1/AMPK signaling-mediated lipid metabolism and inflammation as well as enhanced AKT and NRF2 activation and upregulated downstream antioxidant genes. In summary, exercise attenuates pathological changes in the liver induced by high-fat diets. The underlying mechanisms might be related to NRF2 and mediated by SIRT1/AMPK signaling.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping