Salidroside Attenuates High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease via AMPK-Dependent TXNIP/NLRP3 Pathway
Our previous studies suggested that salidroside could alleviate hepatic steatosis in type 2 diabetic C57BLKS/Leprdb (db/db) mice. The aim of the present study was to evaluate the therapeutic effect of salidroside on high-fat diet- (HFD-) induced nonalcoholic fatty liver disease (NAFLD) by investigat...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Hindawi Limited
2018-01-01
|
Series: | Oxidative Medicine and Cellular Longevity |
Online Access: | http://dx.doi.org/10.1155/2018/8597897 |
id |
doaj-4df0c8717b4c48b8afc724f0bd90e45d |
---|---|
record_format |
Article |
spelling |
doaj-4df0c8717b4c48b8afc724f0bd90e45d2020-11-25T02:33:11ZengHindawi LimitedOxidative Medicine and Cellular Longevity1942-09001942-09942018-01-01201810.1155/2018/85978978597897Salidroside Attenuates High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease via AMPK-Dependent TXNIP/NLRP3 PathwayTao Zheng0Xiaoyan Yang1Wenjin Li2Qibin Wang3Li Chen4Dan Wu5Fang Bian6Shasha Xing7Si Jin8Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaHubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaInstitute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaDepartment of Pharmacy, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, ChinaDepartment of Pharmacy, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, ChinaInstitute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaInstitute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaInstitute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaInstitute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaOur previous studies suggested that salidroside could alleviate hepatic steatosis in type 2 diabetic C57BLKS/Leprdb (db/db) mice. The aim of the present study was to evaluate the therapeutic effect of salidroside on high-fat diet- (HFD-) induced nonalcoholic fatty liver disease (NAFLD) by investigating underlying mechanisms. Mice were fed with HFD or regular diet, randomly divided into two groups, and treated with salidroside or vehicle for 8 weeks. Then, biochemical analyses and histopathological examinations were conducted in vivo and in vitro. Salidroside administration attenuated HFD-induced obesity, blood glucose variability, and hepatic lipid deposition, markedly increasing insulin sensitivity in HFD mice. In addition, salidroside suppressed oxidative stress, thioredoxin-interacting protein (TXNIP) expression, and NLRP3 inflammasome activation in the liver. In cultured hepatocytes, salidroside dose dependently regulated lipid accumulation, reactive oxygen species (ROS) generation, and NLRP3 inflammasome activation as well as improved AMP-activated protein kinase (AMPK) activity and insulin sensitivity. The inhibition of AMPK activation by inhibitor or short interfering RNA (siRNA) resulted in the suppression of the beneficial effects of salidroside in hepatocytes. Our findings demonstrated that salidroside protects against NAFLD by improving hepatic lipid metabolism and NLRP3 inflammasome activation, and these actions are related to the regulation of the oxidative stress and AMPK-dependent TXNIP/NLRP3 pathways.http://dx.doi.org/10.1155/2018/8597897 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Tao Zheng Xiaoyan Yang Wenjin Li Qibin Wang Li Chen Dan Wu Fang Bian Shasha Xing Si Jin |
spellingShingle |
Tao Zheng Xiaoyan Yang Wenjin Li Qibin Wang Li Chen Dan Wu Fang Bian Shasha Xing Si Jin Salidroside Attenuates High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease via AMPK-Dependent TXNIP/NLRP3 Pathway Oxidative Medicine and Cellular Longevity |
author_facet |
Tao Zheng Xiaoyan Yang Wenjin Li Qibin Wang Li Chen Dan Wu Fang Bian Shasha Xing Si Jin |
author_sort |
Tao Zheng |
title |
Salidroside Attenuates High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease via AMPK-Dependent TXNIP/NLRP3 Pathway |
title_short |
Salidroside Attenuates High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease via AMPK-Dependent TXNIP/NLRP3 Pathway |
title_full |
Salidroside Attenuates High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease via AMPK-Dependent TXNIP/NLRP3 Pathway |
title_fullStr |
Salidroside Attenuates High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease via AMPK-Dependent TXNIP/NLRP3 Pathway |
title_full_unstemmed |
Salidroside Attenuates High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease via AMPK-Dependent TXNIP/NLRP3 Pathway |
title_sort |
salidroside attenuates high-fat diet-induced nonalcoholic fatty liver disease via ampk-dependent txnip/nlrp3 pathway |
publisher |
Hindawi Limited |
series |
Oxidative Medicine and Cellular Longevity |
issn |
1942-0900 1942-0994 |
publishDate |
2018-01-01 |
description |
Our previous studies suggested that salidroside could alleviate hepatic steatosis in type 2 diabetic C57BLKS/Leprdb (db/db) mice. The aim of the present study was to evaluate the therapeutic effect of salidroside on high-fat diet- (HFD-) induced nonalcoholic fatty liver disease (NAFLD) by investigating underlying mechanisms. Mice were fed with HFD or regular diet, randomly divided into two groups, and treated with salidroside or vehicle for 8 weeks. Then, biochemical analyses and histopathological examinations were conducted in vivo and in vitro. Salidroside administration attenuated HFD-induced obesity, blood glucose variability, and hepatic lipid deposition, markedly increasing insulin sensitivity in HFD mice. In addition, salidroside suppressed oxidative stress, thioredoxin-interacting protein (TXNIP) expression, and NLRP3 inflammasome activation in the liver. In cultured hepatocytes, salidroside dose dependently regulated lipid accumulation, reactive oxygen species (ROS) generation, and NLRP3 inflammasome activation as well as improved AMP-activated protein kinase (AMPK) activity and insulin sensitivity. The inhibition of AMPK activation by inhibitor or short interfering RNA (siRNA) resulted in the suppression of the beneficial effects of salidroside in hepatocytes. Our findings demonstrated that salidroside protects against NAFLD by improving hepatic lipid metabolism and NLRP3 inflammasome activation, and these actions are related to the regulation of the oxidative stress and AMPK-dependent TXNIP/NLRP3 pathways. |
url |
http://dx.doi.org/10.1155/2018/8597897 |
work_keys_str_mv |
AT taozheng salidrosideattenuateshighfatdietinducednonalcoholicfattyliverdiseaseviaampkdependenttxnipnlrp3pathway AT xiaoyanyang salidrosideattenuateshighfatdietinducednonalcoholicfattyliverdiseaseviaampkdependenttxnipnlrp3pathway AT wenjinli salidrosideattenuateshighfatdietinducednonalcoholicfattyliverdiseaseviaampkdependenttxnipnlrp3pathway AT qibinwang salidrosideattenuateshighfatdietinducednonalcoholicfattyliverdiseaseviaampkdependenttxnipnlrp3pathway AT lichen salidrosideattenuateshighfatdietinducednonalcoholicfattyliverdiseaseviaampkdependenttxnipnlrp3pathway AT danwu salidrosideattenuateshighfatdietinducednonalcoholicfattyliverdiseaseviaampkdependenttxnipnlrp3pathway AT fangbian salidrosideattenuateshighfatdietinducednonalcoholicfattyliverdiseaseviaampkdependenttxnipnlrp3pathway AT shashaxing salidrosideattenuateshighfatdietinducednonalcoholicfattyliverdiseaseviaampkdependenttxnipnlrp3pathway AT sijin salidrosideattenuateshighfatdietinducednonalcoholicfattyliverdiseaseviaampkdependenttxnipnlrp3pathway |
_version_ |
1724815817380462592 |