Improvement of dyslipidemia in OLETF rats by the prostaglandin I(2) analog beraprost sodium.

Abstract

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat was established as an animal model of human type 2 diabetes. Improvement of dyslipidemia by BPS has been confirmed in OLETF rats. The aim of this report is to clarify the mechanisms associated with improvement of dyslipidemia by BPS in OLETF rats. We divided male OLETF rats into three groups; 400microg/kg BPS treated (Group H), 200microg/kg BPS treated (Group L), and untreated control (Group C). After sacrifice, using the quantitative real-time PCR, we assayed the transcription levels of the HMG-CoA reductase (Hmgcr) for cholesterol biosynthesis, monoacylglycerol O-acyltransferase 1 (Mogat1) as TG synthetase, hepatic triglyceride lipase (Lipc) and lipoprotein lipase (Lpl) as triglycerides (TG) reductase in the liver. The mRNA expression of transketolase (Tkt) for pentose phosphate pathway (PPP) enzyme was also evaluated in the liver and kidney. Hmgcr and Mogat1 RNA expression levels were reduced in the livers and those of Tkt were increased in the kidney of BPS treated rats compared with those in untreated rats. The protein expressions of transketolase (Tkt) of BPS treated rats were similarly increased both in the kidney and liver. These results suggest that dyslipidemia was not improved by the acceleration of TG metabolism but by the suppression of activated cholesterol and TG biosyntheses in OLETF rats treated with BPS. High activity of Tkt induced by BPS may be involved in the suppression of such synthetic mechanisms.

• Authors: Maho Watanabe, Hitoshi Nakashima, Kenji Ito, Katsuhisa Miyake, Takao Saito
• Journal: Prostaglandins & other lipid mediators (Prostaglandins Other Lipid Mediat) Vol. 93 Issue 1-2 Pg. 14-9 (Sep 2010) ISSN: 1098-8823 [Print] United States
• PMID: 20450981 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Elsevier Inc. All rights reserved.

Chemical References

• Triglycerides
• beraprost
• Epoprostenol
• Hydroxymethylglutaryl CoA Reductases
• Transketolase
• Acyltransferases
• 2-acylglycerol O-acyltransferase

Topics

• Acyltransferases (genetics, metabolism)
• Animals
• Dyslipidemias (drug therapy, metabolism)
• Epoprostenol (analogs & derivatives, therapeutic use)
• Hydroxymethylglutaryl CoA Reductases (genetics, metabolism)
• Lipid Metabolism
• Male
• Rats
• Rats, Inbred OLETF
• Transketolase (genetics, metabolism)
• Triglycerides (metabolism)