Effects of canagliflozin on weight loss in high-fat diet-induced obese mice

• Published in: PloS one Vol. 12; no. 6; p. e0179960
• Main Authors: Ji, Wenjun, Zhao, Mei, Wang, Meng, Yan, Wenhui, Liu, Yuan, Ren, Shuting, Lu, Jun, Wang, Bing, Chen, Lina
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 30-06-2017; Public Library of Science (PLoS)
• Subjects: Acyltransferase; Animals; Antidiabetics; Biology and Life Sciences; Body weight; Body weight loss; Canagliflozin; Canagliflozin - pharmacology; Cholesterol; Cholesterol - blood; Complications and side effects; Diabetes; Diabetes mellitus; Diacylglycerol O-Acyltransferase - metabolism; Diet; Diet, High-Fat; Dosage and administration; Drug dosages; Drug therapy; Fatty liver; Gene expression; Glucose; Glucose transporter; High fat diet; Hypoglycemic Agents - therapeutic use; Inhibitors; Injury prevention; Lipids; Liver; Liver - drug effects; Liver - pathology; Medicine and Health Sciences; Metabolism; Mice; Mice, Inbred C57BL; mRNA; Obesity; Obesity - enzymology; Obesity - etiology; Obesity - metabolism; Obesity - therapy; Peroxisome proliferator-activated receptors; Peroxisome Proliferator-Activated Receptors - metabolism; Pharmacology; Pharmacy; Rodents; Serum levels; Sodium; Steatosis; Tissues; Triglycerides - blood; Type 2 diabetes; Weight control; Weight loss; Weight Loss - drug effects; Weight reduction; China; Beijing China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0179960

Canagliflozin, an inhibitor of sodium glucose co-transporter (SGLT) 2, has been shown to reduce body weight during the treatment of type 2 diabetes mellitus (T2DM). In this study, we sought to determine the role of canagliflozin in body weight loss and liver injury in obesity. C57BL/6J mice were fed a high-fat diet to simulate diet-induced obesity (DIO). Canagliflozin (15 and 60 mg/kg) was administered to DIO mice for 4 weeks. Orlistat (10 mg/kg) was used as a positive control. The body weight, liver weight, liver morphology, total cholesterol (TC) and triglyceride (TG) levels were examined. Signaling molecules, including diacylgycero1 acyltransferase-2 (DGAT2), peroxisome proliferation receptor alpha-1 (PPARα1), PPARγ1, PPARγ2 mRNA levels and the protein expression of SGLT2 were evaluated. Canagliflozin reduced body weight, especially the high-dose canagliflozin, and resulted in increased body weight loss compared with orlistat. Moreover, canagliflozin reduced the liver weight and the ratio of liver weight to body weight, lowered the serum levels of TC and TG, and ameliorated liver steatosis. During the canagliflozin treatment, SGLT2, DGAT2, PPARγ1 and PPARγ2 were inhibited, and PPARα1 was elevated in the liver tissues. This finding may explain why body weight was reduced and secondary liver injury was ameliorated in response to canagliflozin. Together, the results suggest that canagliflozin may be a potential anti-obesity strategy.