Oxymatrine relieves high-fructose/fat-induced obesity via reprogramming the activity of lipid metabolism-related enhancer
IntroductionEmerging evidence demonstrates that the high-fructose and high-fat diet (HFHF) induced obesity and fatty liver disease has become one of the most common metabolic disorders worldwide. Therefore, innovative investigations on compounds targeting obesity and fatty liver diseases are urgentl...
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1145575/full |
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| author | Luping Ren Xuehua Liu Xuehua Liu Xitong Huang He Zhang Wenjie Fei Xian Yu Zhijuan Hu Yunfeng Zhen Shuchun Chen |
| author_facet | Luping Ren Xuehua Liu Xuehua Liu Xitong Huang He Zhang Wenjie Fei Xian Yu Zhijuan Hu Yunfeng Zhen Shuchun Chen |
| author_sort | Luping Ren |
| collection | DOAJ |
| description | IntroductionEmerging evidence demonstrates that the high-fructose and high-fat diet (HFHF) induced obesity and fatty liver disease has become one of the most common metabolic disorders worldwide. Therefore, innovative investigations on compounds targeting obesity and fatty liver diseases are urgently needed.MethodsThe high-throughput natural compounds screen was performed to screen the important compounds. A rat HFHF model was constructed, the regulatory function of Oxymatrine in HFHF-induced obesity was further explored.ResultsWe identified Oxymatrine, a natural compound extracted from Sophora flavescens, showed a potential compacity in high-fat diet-induced fatty liver disease. We found that oxymatrine significantly inhibited HFHF-induced obesity using a rat HFHF model. Additionally, we found that oxymatrine altered the enhancer landscape of subcutaneous adipose tissues by ChIP-seq analysis using antibodies against the H3K27ac histone modification. Motif enrichment analysis showed the Smad motif was significantly enriched in enhancers altered post-oxymatrine treatment. Further chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) analysis and luciferase reporter assays showed oxymatrine alters the binding of Smad3 on the enhancer regions of B-cell lymphoma 2 (Bcl2) and the enhancer activity of Bcl2.DiscussionTogether, our study highlighted oxymatrine could suppress high-fructose and high-fat diet-induced obesity by inhibiting the suppressor of mothers against decapentaplegic 3 (Smad3) binding on obesity-related enhancers. |
| first_indexed | 2024-03-12T17:33:21Z |
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| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-03-12T17:33:21Z |
| publishDate | 2023-08-01 |
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| series | Frontiers in Endocrinology |
| spelling | doaj.art-27ae034b039648e8aebbbbef7f4f676d2023-08-04T15:40:18ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-08-011410.3389/fendo.2023.11455751145575Oxymatrine relieves high-fructose/fat-induced obesity via reprogramming the activity of lipid metabolism-related enhancerLuping Ren0Xuehua Liu1Xuehua Liu2Xitong Huang3He Zhang4Wenjie Fei5Xian Yu6Zhijuan Hu7Yunfeng Zhen8Shuchun Chen9Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, ChinaDepartment of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, ChinaGraduate School of Hebei North University, Zhangjiakou, Hebei, ChinaDepartment of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing, Jiangsu, ChinaDepartment of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, ChinaDepartment of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, ChinaDepartment of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, ChinaDepartment of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, ChinaDepartment of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, ChinaDepartment of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, ChinaIntroductionEmerging evidence demonstrates that the high-fructose and high-fat diet (HFHF) induced obesity and fatty liver disease has become one of the most common metabolic disorders worldwide. Therefore, innovative investigations on compounds targeting obesity and fatty liver diseases are urgently needed.MethodsThe high-throughput natural compounds screen was performed to screen the important compounds. A rat HFHF model was constructed, the regulatory function of Oxymatrine in HFHF-induced obesity was further explored.ResultsWe identified Oxymatrine, a natural compound extracted from Sophora flavescens, showed a potential compacity in high-fat diet-induced fatty liver disease. We found that oxymatrine significantly inhibited HFHF-induced obesity using a rat HFHF model. Additionally, we found that oxymatrine altered the enhancer landscape of subcutaneous adipose tissues by ChIP-seq analysis using antibodies against the H3K27ac histone modification. Motif enrichment analysis showed the Smad motif was significantly enriched in enhancers altered post-oxymatrine treatment. Further chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) analysis and luciferase reporter assays showed oxymatrine alters the binding of Smad3 on the enhancer regions of B-cell lymphoma 2 (Bcl2) and the enhancer activity of Bcl2.DiscussionTogether, our study highlighted oxymatrine could suppress high-fructose and high-fat diet-induced obesity by inhibiting the suppressor of mothers against decapentaplegic 3 (Smad3) binding on obesity-related enhancers.https://www.frontiersin.org/articles/10.3389/fendo.2023.1145575/fullobesityoxymatrineSmad3enhancerfatty liver disease |
| spellingShingle | Luping Ren Xuehua Liu Xuehua Liu Xitong Huang He Zhang Wenjie Fei Xian Yu Zhijuan Hu Yunfeng Zhen Shuchun Chen Oxymatrine relieves high-fructose/fat-induced obesity via reprogramming the activity of lipid metabolism-related enhancer Frontiers in Endocrinology obesity oxymatrine Smad3 enhancer fatty liver disease |
| title | Oxymatrine relieves high-fructose/fat-induced obesity via reprogramming the activity of lipid metabolism-related enhancer |
| title_full | Oxymatrine relieves high-fructose/fat-induced obesity via reprogramming the activity of lipid metabolism-related enhancer |
| title_fullStr | Oxymatrine relieves high-fructose/fat-induced obesity via reprogramming the activity of lipid metabolism-related enhancer |
| title_full_unstemmed | Oxymatrine relieves high-fructose/fat-induced obesity via reprogramming the activity of lipid metabolism-related enhancer |
| title_short | Oxymatrine relieves high-fructose/fat-induced obesity via reprogramming the activity of lipid metabolism-related enhancer |
| title_sort | oxymatrine relieves high fructose fat induced obesity via reprogramming the activity of lipid metabolism related enhancer |
| topic | obesity oxymatrine Smad3 enhancer fatty liver disease |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1145575/full |
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