Discovery of a Potent 9-Deazaxanthine-based Agent for the Treatment of Obesity-Related Non-alcoholic Fatty Liver Disease.
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.
['Chen|Jinying|J|', 'Ma|Liang|L|', 'Huang|Li|L|', 'Xie|Caifeng|C|', 'Pei|Heying|H|', 'He|Linhong|L|', 'Fu|Suhong|S|', 'Chen|Lijuan|L|']
D041721:3T3-L1 Cells D052242:Adiponectin D000818:Animals D008078:Cholesterol, LDL D055808:Drug Discovery D005786:Gene Expression Regulation D056945:Hep G2 Cells D006801:Humans D020738:Leptin D008297:Male D051379:Mice D065626:Non-alcoholic Fatty Liver Disease D009765:Obesity D051381:Rats D017208:Rats, Wistar D014280:Triglycerides D014970:Xanthines
adiponectin leptin NAFLD OGTT diet-induced obesity glucose lowering