Ipragliflozin, an SGLT2 inhibitor, exhibits a prophylactic effect on hepatic steatosis and fibrosis induced by choline-deficient l-amino acid-defined diet in rats.

Abstract

Ipragliflozin is a selective sodium glucose cotransporter 2 (SGLT2) inhibitor that increases urinary glucose excretion by inhibiting renal glucose reabsorption and thereby causes a subsequent antihyperglycemic effect. As nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH), is closely linked to metabolic diseases such as obesity and diabetes, we investigated the effect of ipragliflozin on NAFLD in rats fed a choline-deficient l-amino acid-defined (CDAA) diet. Five weeks after starting the CDAA diet, rats exhibited hepatic triglyceride (TG) accumulation, fibrosis, and mild inflammation. Repeated oral administration of ipragliflozin (3mg/g, once daily for 5 weeks) prevented both hepatic TG accumulation (188 vs.290 mg/g tissue vehicle-treated group; P<0.001) and large lipid droplet formation. Further, ipragliflozin exerted a prophylactic effect on liver fibrosis, as indicated by a marked decrease in hydroxyproline content and fibrosis score. Pioglitazone, which is known to be effective on hepatic fibrosis in CDAA diet-fed rats as well as NASH patients with type 2 diabetes mellitus (T2DM), also exerted a mild prophylactic effect on fibrosis, but not on hepatic TG accumulation or inflammation. In conclusion, ipragliflozin prevented hepatic TG accumulation and fibrosis in CDAA-diet rats. These findings suggest the therapeutic potential of ipragliflozin for patients with NAFLD.

• Authors: Yuka Hayashizaki-Someya, Eiji Kurosaki, Toshiyuki Takasu, Hikaru Mitori, Shunji Yamazaki, Kumi Koide, Shoji Takakura
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 754 Pg. 19-24 (May 05 2015) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 25701721 (Publication Type: Journal Article)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Amino Acids
• Glucosides
• Hypoglycemic Agents
• Sodium-Glucose Transporter 2 Inhibitors
• Thiazolidinediones
• Thiophenes
• Triglycerides
• ipragliflozin
• Hydroxyproline
• Pioglitazone

Topics

• Amino Acids (pharmacology)
• Animals
• Choline Deficiency (complications, drug therapy, pathology)
• Food, Formulated (adverse effects)
• Glucosides (pharmacology, therapeutic use)
• Hydroxyproline (metabolism)
• Hypoglycemic Agents (pharmacology, therapeutic use)
• Inflammation (chemically induced, complications, prevention & control)
• Liver Cirrhosis (chemically induced, complications, pathology, prevention & control)
• Male
• Non-alcoholic Fatty Liver Disease (chemically induced, complications, metabolism, prevention & control)
• Pioglitazone
• Rats
• Sodium-Glucose Transporter 2 Inhibitors
• Thiazolidinediones (therapeutic use)
• Thiophenes (pharmacology, therapeutic use)
• Triglycerides (metabolism)