Differential modulatory effects of rosiglitazone and pioglitazone on white adipose tissue in db/db mice

Aims: This study was performed to clarify the different action mechanisms through which rosiglitazone and pioglitazone regulate lipogenesis in white adipose tissues of db/db mice, an animal model of diabetes. Main methods: Male C57BLKS/J-Lepr(db/db) (db/db) mice were used for all experiments. Rosiglitazone or pioglitazone were administered once daily by oral gavage for 4 weeks at concentrations of 20 mg/kg and 75 mg/kg, respectively. At 0, 3, 6, 9, 12, 15, 21, and 28 days of administration, body weights and blood glucose were determined. At the end of experiment, adiposity and gene expression were confirmed by perilipin A immunostaining and real-time PCR. Key findings: Pioglitazone treatment increased fat mass and the surface area of adipocytes more than rosiglitazone at dosages with equivalent effects on plasma glucose. Lipid parameters including plasma total cholesterol and triglycerides were decreased more in rosiglitazone-treated mice. Relative mRNA expression levels for lipid synthesis and transport including diacylglycerol acyltransferase (DGAT1/2), fatty acid translocase (CD36/FAT), fatty acid transport protein (FATP) were increased in pioglitazone-treated group compared to rosiglitazone-treated mice, but mRNA expression levels of beta-oxidation-related genes acyl-Coenzyme A dehydrogenase, very long chain (Acadvl), acyl-Coenzyme A dehydrogenase, medium chain (Acadm), and the energy expenditure-related genes triosephosphate isomerase 1 (Tpi1) and carnitine palmitoyltransferase 1b (Cpt1b) were decreased. Significance: These results suggest that pioglitazone activates lipid deposition by increasing lipid synthesis and transport, but rosiglitazone stimulates beta-oxidation and energy expenditure in adipocytes of db/db mice. (C) 2010 Elsevier Inc. All rights reserved.