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论文题目: Anhydroicaritin improves diet-induced obesity and hyperlipidemia and alleviates insulin resistance by suppressing SREBPs activation
英文论文题目: Anhydroicaritin improves diet-induced obesity and hyperlipidemia and alleviates insulin resistance by suppressing SREBPs activation
第一作者: Zheng, ZG; Zhou, YP; Zhang, X; Thu, PM; Xie, ZS; Lu, C; Pang, T; Xue, B; Xu, DQ; Chen, Y; Chen, XW; Li, HJ; Xu, XJ
英文第一作者: Zheng, ZG; Zhou, YP; Zhang, X; Thu, PM; Xie, ZS; Lu, C; Pang, T; Xue, B; Xu, DQ; Chen, Y; Chen, XW; Li, HJ; Xu, XJ
联系作者: Li, HJ; Xu, XJ (reprint author), China Pharmaceut Univ, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China.
英文联系作者: Li, HJ; Xu, XJ (reprint author), China Pharmaceut Univ, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China.
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发表年度: 2016
卷: 122
期:
页码: 42-61
摘要: SREBPs play important roles in the regulation of lipid metabolism, and are closely related to the occurrence and development of many metabolic diseases. Small molecular inhibitors of SERBPs are important tools in developing efficient treatment of metabolic diseases. However, there are no listing drug targeting SREBP5. Therefore, there is an urgent need to develop highly specific small molecules that inhibit SREBP5. In this study, using a hepatocyte-based high-throughput screening, we identified anhydroicaritin (AHI) as a novel inhibitor of SREBPs. HepG2, HL-7702, and human primary hepatocytes were used to verify the effects of AHI. We explored the mechanism by which AHI blocks the binding of SCAP/SREBPs complex with Sec23 alpha/24D via regulating LKB1/AMPK/mTOR pathway. AHI reduced liver cell lipid level by preventing de novo lipogenesis. In diet induced obese mice, AHI ameliorated obesity, insulin resistance, fatty accumulation in liver and hyperlipemia. In conclusion, AHI improves diet-induced obesity and alleviates insulin resistance by suppressing SREBPs maturation which is dependent on LKB1/AMPK/mTOR pathway. Thus, AHI can serve as a leading compound for pharmacological control of metabolic diseases.
英文摘要: SREBPs play important roles in the regulation of lipid metabolism, and are closely related to the occurrence and development of many metabolic diseases. Small molecular inhibitors of SERBPs are important tools in developing efficient treatment of metabolic diseases. However, there are no listing drug targeting SREBP5. Therefore, there is an urgent need to develop highly specific small molecules that inhibit SREBP5. In this study, using a hepatocyte-based high-throughput screening, we identified anhydroicaritin (AHI) as a novel inhibitor of SREBPs. HepG2, HL-7702, and human primary hepatocytes were used to verify the effects of AHI. We explored the mechanism by which AHI blocks the binding of SCAP/SREBPs complex with Sec23 alpha/24D via regulating LKB1/AMPK/mTOR pathway. AHI reduced liver cell lipid level by preventing de novo lipogenesis. In diet induced obese mice, AHI ameliorated obesity, insulin resistance, fatty accumulation in liver and hyperlipemia. In conclusion, AHI improves diet-induced obesity and alleviates insulin resistance by suppressing SREBPs maturation which is dependent on LKB1/AMPK/mTOR pathway. Thus, AHI can serve as a leading compound for pharmacological control of metabolic diseases.
刊物名称: BIOCHEMICAL PHARMACOLOGY
英文刊物名称: BIOCHEMICAL PHARMACOLOGY
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学科: Pharmacology & Pharmacy
英文学科: Pharmacology & Pharmacy
影响因子: 4.581
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论文类别: Article
英文论文类别: Article
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