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...
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| Format: | Article |
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.826628/full |
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| author | Fei Zhou Mingning Ding Yiqing Gu Guifang Fan Chuanyang Liu Yijie Li Rong Sun Rong Sun Jianzhi Wu Jianchao Li Jianchao Li Xiaoyong Xue Hongjuan Li Xiaojiaoyang Li |
| author_facet | Fei Zhou Mingning Ding Yiqing Gu Guifang Fan Chuanyang Liu Yijie Li Rong Sun Rong Sun Jianzhi Wu Jianchao Li Jianchao Li Xiaoyong Xue Hongjuan Li Xiaojiaoyang Li |
| author_sort | Fei Zhou |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-18T05:30:32Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-18T05:30:32Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-ec8e59eacb7748d39749f85ef683b0642022-12-21T21:19:27ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-01-011210.3389/fphar.2021.826628826628Aurantio-Obtusin Attenuates Non-Alcoholic Fatty Liver Disease Through AMPK-Mediated Autophagy and Fatty Acid Oxidation PathwaysFei Zhou0Mingning Ding1Yiqing Gu2Guifang Fan3Chuanyang Liu4Yijie Li5Rong Sun6Rong Sun7Jianzhi Wu8Jianchao Li9Jianchao Li10Xiaoyong Xue11Hongjuan Li12Xiaojiaoyang Li13School of Life Sciences, Beijing University of Chinese Medicine, Beijing, ChinaSchool of Life Sciences, Beijing University of Chinese Medicine, Beijing, ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, ChinaSchool of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, ChinaSchool of Life Sciences, Beijing University of Chinese Medicine, Beijing, ChinaThe Second Hospital of University, Jinan, ChinaAdvanced Medical Research Institute, Shandong University, Jinan, ChinaSchool of Life Sciences, Beijing University of Chinese Medicine, Beijing, ChinaThe Second Hospital of University, Jinan, ChinaShandong University of Traditional Chinese Medicine, Jinan, ChinaSchool of Life Sciences, Beijing University of Chinese Medicine, Beijing, ChinaSchool of Life Sciences, Beijing University of Chinese Medicine, Beijing, ChinaSchool of Life Sciences, Beijing University of Chinese Medicine, Beijing, ChinaNonalcoholic 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.https://www.frontiersin.org/articles/10.3389/fphar.2021.826628/fullaurantio-obtusinnonalcoholic fatty liver diseaseautophagyAMPKPPARαACOX1 |
| spellingShingle | Fei Zhou Mingning Ding Yiqing Gu Guifang Fan Chuanyang Liu Yijie Li Rong Sun Rong Sun Jianzhi Wu Jianchao Li Jianchao Li Xiaoyong Xue Hongjuan Li Xiaojiaoyang Li Aurantio-Obtusin Attenuates Non-Alcoholic Fatty Liver Disease Through AMPK-Mediated Autophagy and Fatty Acid Oxidation Pathways Frontiers in Pharmacology aurantio-obtusin nonalcoholic fatty liver disease autophagy AMPK PPARα ACOX1 |
| 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 | aurantio-obtusin nonalcoholic fatty liver disease autophagy AMPK PPARα ACOX1 |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.826628/full |
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