Cargando…
Aurantio-Obtusin Attenuates Non-Alcoholic Fatty Liver Disease Through AMPK-Mediated Autophagy and Fatty Acid Oxidation Pathways
Nonalcoholic fatty liver disease (NAFLD), manifested as the aberrant accumulation of lipids in hepatocytes and inflammation, has become an important cause of advanced liver diseases and hepatic malignancies worldwide. However, no effective therapy has been approved yet. Aurantio-obtusin (AO) is a ma...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8787202/ https://www.ncbi.nlm.nih.gov/pubmed/35087411 http://dx.doi.org/10.3389/fphar.2021.826628 |
_version_ | 1784639308981862400 |
---|---|
author | Zhou, Fei Ding, Mingning Gu, Yiqing Fan, Guifang Liu, Chuanyang Li, Yijie Sun, Rong Wu, Jianzhi Li, Jianchao Xue, Xiaoyong Li, Hongjuan Li, Xiaojiaoyang |
author_facet | Zhou, Fei Ding, Mingning Gu, Yiqing Fan, Guifang Liu, Chuanyang Li, Yijie Sun, Rong Wu, Jianzhi Li, Jianchao Xue, Xiaoyong Li, Hongjuan Li, Xiaojiaoyang |
author_sort | Zhou, Fei |
collection | PubMed |
description | Nonalcoholic fatty liver disease (NAFLD), manifested as the aberrant accumulation of lipids in hepatocytes and inflammation, has become an important cause of advanced liver diseases and hepatic malignancies worldwide. However, no effective therapy has been approved yet. Aurantio-obtusin (AO) is a main bioactive compound isolated from Cassia semen that has been identified with multiple pharmacological activities, including improving adiposity and insulin resistance. However, the ameliorating effects of AO on diet-induced NAFLD and underlying mechanisms remained poorly elucidated. Our results demonstrated that AO significantly alleviated high-fat diet and glucose-fructose water (HFSW)-induced hepatic steatosis in mice and oleic acid and palmitic acid (OAPA)-induced lipid accumulation in hepatocytes. Remarkably, AO was found to distinctly promote autophagy flux and influence the degradation of lipid droplets by inducing AMPK phosphorylation. Additionally, the induction of AMPK triggered TFEB activation and promoted fatty acid oxidation (FAO) by activating PPARα and ACOX1 and decreasing the expression of genes involved in lipid biosynthesis. Meanwhile, the lipid-lowing effect of AO was significantly prevented by the pretreatment with inhibitors of autophagy, PPARα or ACOX1, respectively. Collectively, our study suggests that AO ameliorates hepatic steatosis via AMPK/autophagy- and AMPK/TFEB-mediated suppression of lipid accumulation, which opens new opportunities for pharmacological treatment of NAFLD and associated complications. |
format | Online Article Text |
id | pubmed-8787202 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-87872022022-01-26 Aurantio-Obtusin Attenuates Non-Alcoholic Fatty Liver Disease Through AMPK-Mediated Autophagy and Fatty Acid Oxidation Pathways Zhou, Fei Ding, Mingning Gu, Yiqing Fan, Guifang Liu, Chuanyang Li, Yijie Sun, Rong Wu, Jianzhi Li, Jianchao Xue, Xiaoyong Li, Hongjuan Li, Xiaojiaoyang Front Pharmacol Pharmacology Nonalcoholic fatty liver disease (NAFLD), manifested as the aberrant accumulation of lipids in hepatocytes and inflammation, has become an important cause of advanced liver diseases and hepatic malignancies worldwide. However, no effective therapy has been approved yet. Aurantio-obtusin (AO) is a main bioactive compound isolated from Cassia semen that has been identified with multiple pharmacological activities, including improving adiposity and insulin resistance. However, the ameliorating effects of AO on diet-induced NAFLD and underlying mechanisms remained poorly elucidated. Our results demonstrated that AO significantly alleviated high-fat diet and glucose-fructose water (HFSW)-induced hepatic steatosis in mice and oleic acid and palmitic acid (OAPA)-induced lipid accumulation in hepatocytes. Remarkably, AO was found to distinctly promote autophagy flux and influence the degradation of lipid droplets by inducing AMPK phosphorylation. Additionally, the induction of AMPK triggered TFEB activation and promoted fatty acid oxidation (FAO) by activating PPARα and ACOX1 and decreasing the expression of genes involved in lipid biosynthesis. Meanwhile, the lipid-lowing effect of AO was significantly prevented by the pretreatment with inhibitors of autophagy, PPARα or ACOX1, respectively. Collectively, our study suggests that AO ameliorates hepatic steatosis via AMPK/autophagy- and AMPK/TFEB-mediated suppression of lipid accumulation, which opens new opportunities for pharmacological treatment of NAFLD and associated complications. Frontiers Media S.A. 2022-01-11 /pmc/articles/PMC8787202/ /pubmed/35087411 http://dx.doi.org/10.3389/fphar.2021.826628 Text en Copyright © 2022 Zhou, Ding, Gu, Fan, Liu, Li, Sun, Wu, Li, Xue, Li and Li. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Zhou, Fei Ding, Mingning Gu, Yiqing Fan, Guifang Liu, Chuanyang Li, Yijie Sun, Rong Wu, Jianzhi Li, Jianchao Xue, Xiaoyong Li, Hongjuan Li, Xiaojiaoyang Aurantio-Obtusin Attenuates Non-Alcoholic Fatty Liver Disease Through AMPK-Mediated Autophagy and Fatty Acid Oxidation Pathways |
title | Aurantio-Obtusin Attenuates Non-Alcoholic Fatty Liver Disease Through AMPK-Mediated Autophagy and Fatty Acid Oxidation Pathways |
title_full | Aurantio-Obtusin Attenuates Non-Alcoholic Fatty Liver Disease Through AMPK-Mediated Autophagy and Fatty Acid Oxidation Pathways |
title_fullStr | Aurantio-Obtusin Attenuates Non-Alcoholic Fatty Liver Disease Through AMPK-Mediated Autophagy and Fatty Acid Oxidation Pathways |
title_full_unstemmed | Aurantio-Obtusin Attenuates Non-Alcoholic Fatty Liver Disease Through AMPK-Mediated Autophagy and Fatty Acid Oxidation Pathways |
title_short | Aurantio-Obtusin Attenuates Non-Alcoholic Fatty Liver Disease Through AMPK-Mediated Autophagy and Fatty Acid Oxidation Pathways |
title_sort | aurantio-obtusin attenuates non-alcoholic fatty liver disease through ampk-mediated autophagy and fatty acid oxidation pathways |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8787202/ https://www.ncbi.nlm.nih.gov/pubmed/35087411 http://dx.doi.org/10.3389/fphar.2021.826628 |
work_keys_str_mv | AT zhoufei aurantioobtusinattenuatesnonalcoholicfattyliverdiseasethroughampkmediatedautophagyandfattyacidoxidationpathways AT dingmingning aurantioobtusinattenuatesnonalcoholicfattyliverdiseasethroughampkmediatedautophagyandfattyacidoxidationpathways AT guyiqing aurantioobtusinattenuatesnonalcoholicfattyliverdiseasethroughampkmediatedautophagyandfattyacidoxidationpathways AT fanguifang aurantioobtusinattenuatesnonalcoholicfattyliverdiseasethroughampkmediatedautophagyandfattyacidoxidationpathways AT liuchuanyang aurantioobtusinattenuatesnonalcoholicfattyliverdiseasethroughampkmediatedautophagyandfattyacidoxidationpathways AT liyijie aurantioobtusinattenuatesnonalcoholicfattyliverdiseasethroughampkmediatedautophagyandfattyacidoxidationpathways AT sunrong aurantioobtusinattenuatesnonalcoholicfattyliverdiseasethroughampkmediatedautophagyandfattyacidoxidationpathways AT wujianzhi aurantioobtusinattenuatesnonalcoholicfattyliverdiseasethroughampkmediatedautophagyandfattyacidoxidationpathways AT lijianchao aurantioobtusinattenuatesnonalcoholicfattyliverdiseasethroughampkmediatedautophagyandfattyacidoxidationpathways AT xuexiaoyong aurantioobtusinattenuatesnonalcoholicfattyliverdiseasethroughampkmediatedautophagyandfattyacidoxidationpathways AT lihongjuan aurantioobtusinattenuatesnonalcoholicfattyliverdiseasethroughampkmediatedautophagyandfattyacidoxidationpathways AT lixiaojiaoyang aurantioobtusinattenuatesnonalcoholicfattyliverdiseasethroughampkmediatedautophagyandfattyacidoxidationpathways |