Exercise Intervention Mitigates Pathological Liver Changes in NAFLD Zebrafish by Activating SIRT1/AMPK/NRF2 Signaling

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 st...

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Main Authors: Yunyi Zou, Zhanglin Chen, Chenchen Sun, Dong Yang, Zuoqiong Zhou, Xiyang Peng, Lan Zheng, Changfa Tang
Format: Article
Language:English
Published: MDPI AG 2021-10-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/20/10940
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author Yunyi Zou
Zhanglin Chen
Chenchen Sun
Dong Yang
Zuoqiong Zhou
Xiyang Peng
Lan Zheng
Changfa Tang
author_facet Yunyi Zou
Zhanglin Chen
Chenchen Sun
Dong Yang
Zuoqiong Zhou
Xiyang Peng
Lan Zheng
Changfa Tang
author_sort Yunyi Zou
collection DOAJ
description 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 <i>bcl2</i> and decreased the expression of genes associated with apoptosis (<i>caspase3</i>, <i>bax</i>). 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.
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spelling doaj.art-1974420b6af64174969f753bf644a2942023-11-22T18:31:06ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-10-0122201094010.3390/ijms222010940Exercise Intervention Mitigates Pathological Liver Changes in NAFLD Zebrafish by Activating SIRT1/AMPK/NRF2 SignalingYunyi Zou0Zhanglin Chen1Chenchen Sun2Dong Yang3Zuoqiong Zhou4Xiyang Peng5Lan Zheng6Changfa Tang7Key Laboratory of Physical Fitness and Exercise Rehabilitation of Hunan Province, College of Physical Education, Hunan Normal University, Changsha 410012, ChinaKey Laboratory of Physical Fitness and Exercise Rehabilitation of Hunan Province, College of Physical Education, Hunan Normal University, Changsha 410012, ChinaKey Laboratory of Physical Fitness and Exercise Rehabilitation of Hunan Province, College of Physical Education, Hunan Normal University, Changsha 410012, ChinaKey Laboratory of Physical Fitness and Exercise Rehabilitation of Hunan Province, College of Physical Education, Hunan Normal University, Changsha 410012, ChinaKey Laboratory of Physical Fitness and Exercise Rehabilitation of Hunan Province, College of Physical Education, Hunan Normal University, Changsha 410012, ChinaKey Laboratory of Physical Fitness and Exercise Rehabilitation of Hunan Province, College of Physical Education, Hunan Normal University, Changsha 410012, ChinaKey Laboratory of Physical Fitness and Exercise Rehabilitation of Hunan Province, College of Physical Education, Hunan Normal University, Changsha 410012, ChinaKey Laboratory of Physical Fitness and Exercise Rehabilitation of Hunan Province, College of Physical Education, Hunan Normal University, Changsha 410012, ChinaNon-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 <i>bcl2</i> and decreased the expression of genes associated with apoptosis (<i>caspase3</i>, <i>bax</i>). 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.https://www.mdpi.com/1422-0067/22/20/10940zebrafishNAFLDexerciseROSSIRT1/AMPK/NRF2
spellingShingle Yunyi Zou
Zhanglin Chen
Chenchen Sun
Dong Yang
Zuoqiong Zhou
Xiyang Peng
Lan Zheng
Changfa Tang
Exercise Intervention Mitigates Pathological Liver Changes in NAFLD Zebrafish by Activating SIRT1/AMPK/NRF2 Signaling
International Journal of Molecular Sciences
zebrafish
NAFLD
exercise
ROS
SIRT1/AMPK/NRF2
title Exercise Intervention Mitigates Pathological Liver Changes in NAFLD Zebrafish by Activating SIRT1/AMPK/NRF2 Signaling
title_full Exercise Intervention Mitigates Pathological Liver Changes in NAFLD Zebrafish by Activating SIRT1/AMPK/NRF2 Signaling
title_fullStr Exercise Intervention Mitigates Pathological Liver Changes in NAFLD Zebrafish by Activating SIRT1/AMPK/NRF2 Signaling
title_full_unstemmed Exercise Intervention Mitigates Pathological Liver Changes in NAFLD Zebrafish by Activating SIRT1/AMPK/NRF2 Signaling
title_short Exercise Intervention Mitigates Pathological Liver Changes in NAFLD Zebrafish by Activating SIRT1/AMPK/NRF2 Signaling
title_sort exercise intervention mitigates pathological liver changes in nafld zebrafish by activating sirt1 ampk nrf2 signaling
topic zebrafish
NAFLD
exercise
ROS
SIRT1/AMPK/NRF2
url https://www.mdpi.com/1422-0067/22/20/10940
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AT dongyang exerciseinterventionmitigatespathologicalliverchangesinnafldzebrafishbyactivatingsirt1ampknrf2signaling
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AT lanzheng exerciseinterventionmitigatespathologicalliverchangesinnafldzebrafishbyactivatingsirt1ampknrf2signaling
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