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Discovery of a Potent 9-Deazaxanthine-based Agent for the Treatment of Obesity-Related Non-alcoholic Fatty Liver Disease.

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机构： [1]Division of Nephrology, Kidney Research Institute, West China Hospital, Sichuan University, Chengdu 610041, China [2]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China

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关键词： adiponectin diet-induced obesity glucose lowering leptin NAFLD OGTT

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A series of deazaxanthine-based derivatives were rationally prepared and evaluated. 8g exhibited the most potent glucose-lowering effect on HepG2 cell line and modulated adiponectin and leptin expression in 3T3-L1 adipocytes. Oral administration of 8g at 25 mg/kg/day for 4 weeks manifested therapeutic effects on high-fat diet-induced non-alcoholic fatty liver disease (NAFLD) by decreasing the weights of the body, liver, and fat. 8g also modulated the serum levels of fasting glucose and adiponectin, triglycerides, low-density lipoprotein-cholesterol, and alanine aminotransferase, as well as the hepatic concentrations of triglycerides, total cholesterol. Moreover, 8g significantly decreased steatosis and blocked the increase of adipocytes and the size of adipose tissues from NAFLD. In the DIO mice model, 8g ameliorated the obesity-related symptoms and normalized serum biomarkers. © 2014 John Wiley & Sons A/S.

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出版当年[2015]版：

大类 | 3 区医学

小类 | 3 区药物化学 4 区生化与分子生物学

最新[2023]版：

大类 | 4 区医学

小类 | 4 区生化与分子生物学 4 区药物化学

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第一作者机构： [1]Division of Nephrology, Kidney Research Institute, West China Hospital, Sichuan University, Chengdu 610041, China [2]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China

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