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...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhou, Fei, Ding, Mingning, Gu, Yiqing, Fan, Guifang, Liu, Chuanyang, Li, Yijie, Sun, Rong, Wu, Jianzhi, Li, Jianchao, Xue, Xiaoyong, Li, Hongjuan, Li, Xiaojiaoyang
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