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


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 20mg/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.


RESULTS
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 β-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.


CONCLUSIONS
these results suggest that pioglitazone activates lipid deposition by increasing lipid synthesis and transport, but rosiglitazone stimulates β-oxidation and energy expenditure in adipocytes of db/db mice.
Yang
Keum-Jin
KJ
Animal Model Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 111 Gwahangno, Yuseong-gu, Daejeon 305-806, South Korea.
Noh
Jung-Ran
JR
Kim
Yong-Hoon
YH
Gang
Gil-Tae
GT
Hwang
Jung-Hwan
JH
Yang
Suk Jin
SJ
Yeom
Young Il
YI
Lee
Chul-Ho
CH
D042964:Acyl-CoA Dehydrogenase / Q000235:genetics / Q000378:metabolism; D052436:Adipose Tissue, White / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D051048:Diacylglycerol O-Acyltransferase / Q000235:genetics / Q000378:metabolism; D050612:Fatty Acid Transport Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000077205:Pioglitazone; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D018955:CD36 Antigens; D050612:Fatty Acid Transport Proteins; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D014280:Triglycerides; D000077154:Rosiglitazone; D002784:Cholesterol; D042964:Acyl-CoA Dehydrogenase; D051048:Diacylglycerol O-Acyltransferase; D000077205:Pioglitazone