title: Discovery of a Potent 9-Deazaxanthine-based Agent for the Treatment of Obesity-Related Non-alcoholic Fatty Liver Disease.
abstract: 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.
authors.affiliation: Division of Nephrology, Kidney Research Institute, West China Hospital, Sichuan University, Chengdu, 610041, China.|State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China.
authors.forename: Jinying
authors.initials: J
authors.lastname: Chen
authors.affiliation: Division of Nephrology, Kidney Research Institute, West China Hospital, Sichuan University, Chengdu, 610041, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China.
authors.forename: Li
authors.initials: L
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China.
authors.forename: Caifeng
authors.initials: C
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China.
authors.forename: Heying
authors.initials: H
authors.lastname: Pei
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China.
authors.forename: Linhong
authors.initials: L
authors.lastname: He
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China.
authors.forename: Suhong
authors.initials: S
authors.lastname: Fu
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Chen
mesh_terms: D041721:3T3-L1 Cells; D052242:Adiponectin / Q000097:blood; D000818:Animals; D008078:Cholesterol, LDL / Q000097:blood; D055808:Drug Discovery; D005786:Gene Expression Regulation / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D020738:Leptin / Q000097:blood; D008297:Male; D051379:Mice; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000188:drug therapy*; D009765:Obesity / Q000097:blood / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000097:blood; D014970:Xanthines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; C499919:Adipoq protein, mouse; D008078:Cholesterol, LDL; D020738:Leptin; D014280:Triglycerides; D014970:Xanthines
keywords: NAFLD; OGTT; adiponectin; diet-induced obesity; glucose lowering; leptin