Lipoprotein lipase activator NO-1886 (ibrolipim) accelerates the mRNA expression of fatty acid oxidation-related enzymes in rat liver.
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.
Doi
Masako
M
Division of Pharmacology, Drug Safety and Metabolism, and Research and Development, Otsuka Pharmaceutical Factory, Inc., Naruto, Tokushima, Japan.
Kondo
Yasunori
Y
Tsutsumi
Kazuhiko
K
D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D002245:Carbon Dioxide / Q000097:blood; D017931:DNA Primers; D020536:Enzyme Activators / Q000494:pharmacology*; D005227:Fatty Acids / Q000378:metabolism*; D007473:Ion Channels; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D026901:Membrane Transport Proteins / Q000096:biosynthesis; D024101:Mitochondrial Proteins / Q000096:biosynthesis; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071246:Uncoupling Protein 2
D001549:Benzamides; D017931:DNA Primers; D020536:Enzyme Activators; D005227:Fatty Acids; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D009943:Organophosphorus Compounds; D012333:RNA, Messenger; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2; C082137:4-diethoxyphosphorylmethyl-N-(4-bromo-2-cyanophenyl)benzamide; D002245:Carbon Dioxide; D008071:Lipoprotein Lipase