Lipoprotein lipase activator NO-1886 (ibrolipim) accelerates the mRNA expression of fatty acid oxidation-related enzymes in rat liver.

Abstract

The lipoprotein lipase (LPL) activator NO-1886 (ibrolipim) has been shown to have potential benefits for the treatment of obesity in rats. However, the anti-obesity mechanism of NO-1886 has not been clearly understood. To address this, we studied the effects of NO-1886 on the mRNA expression of fatty acid oxidation-related enzymes in rats. The respiratory quotient (RQ) in rats administered a single oral dose of NO-1886 was significantly lower than control rats under both fed and fasted conditions. NO-1886 orally administered to rats for 7 days caused 1.54-fold increase in carnitine palmitoyl transferase II (CPTII) mRNA in the carnitine palmitoyl transferase system. Furthermore, NO-1886 caused a 1.47-fold increase in long-chain acyl-CoA dehydrogenase (LCAD) mRNA, a 1.49-fold increase in acetyl-CoA acyltransferase 2 (ACAA2) mRNA, and a 1.24-fold increase in enoyl-CoA hydratase (ECH) mRNA in rats, all which are liver beta-oxidation enzymes. NO-1886 also increased uncoupling protein-2 (UCP2) mRNA levels in liver by 1.42-fold when compared to the control group. These results suggest that the LPL activator NO-1886 may accelerate the expression of fatty acid oxidation-related enzymes, resulting in a reduction of RQ.

• Authors: Masako Doi, Yasunori Kondo, Kazuhiko Tsutsumi
• Journal: Metabolism: clinical and experimental (Metabolism) Vol. 52 Issue 12 Pg. 1547-50 (Dec 2003) ISSN: 0026-0495 [Print] United States
• PMID: 14669153 (Publication Type: Journal Article)

Chemical References

• Benzamides
• DNA Primers
• Enzyme Activators
• Fatty Acids
• Ion Channels
• Membrane Transport Proteins
• Mitochondrial Proteins
• Organophosphorus Compounds
• RNA, Messenger
• Ucp2 protein, rat
• Uncoupling Protein 2
• 4-diethoxyphosphorylmethyl-N-(4-bromo-2-cyanophenyl)benzamide
• Carbon Dioxide
• Lipoprotein Lipase

Topics

• Animals
• Benzamides (pharmacology)
• Carbon Dioxide (blood)
• DNA Primers
• Enzyme Activators (pharmacology)
• Fatty Acids (metabolism)
• Ion Channels
• Lipoprotein Lipase (metabolism)
• Liver (drug effects, enzymology)
• Male
• Membrane Transport Proteins (biosynthesis)
• Mitochondrial Proteins (biosynthesis)
• Organophosphorus Compounds (pharmacology)
• Oxidation-Reduction
• Oxygen Consumption (drug effects)
• RNA, Messenger (biosynthesis)
• Rats
• Rats, Sprague-Dawley
• Reverse Transcriptase Polymerase Chain Reaction
• Uncoupling Protein 2