NO-1886 (ibrolipim), a lipoprotein lipase-promoting agent, accelerates the expression of UCP3 messenger RNA and ameliorates obesity in ovariectomized rats.
The synthetic compound NO-1886 (ibrolipim, [4-(4-bromo-2-cyano-phenylcarbamoyl)-benzyl]-phosphonic acid diethyl ester, CAS 133208-93-2) is a lipoprotein lipase (LPL)-promoting agent that decreases plasma triglycerides, increases high-density lipoprotein cholesterol levels, and prevents fat accumulation in high fat-fed rats. However, the effect of NO-1886 on body weight, fat accumulation, and energy expenditure in ovariectomized (OVX) rats is not clear. The primary aim of this study was to ascertain whether NO-1886 ameliorated obesity in OVX rats and to examine the effects on fatty acid oxidation-related enzymes. NO-1886 decreased accumulation of visceral fat and suppressed the increase in body weight resulting from the ovariectomy. NO-1886 decreased the respiratory quotient and increased expression of the fatty acid translocase messenger RNA (mRNA) in the liver, soleus muscle, and mesenteric fat. NO-1886 also increased the expression of fatty acid-binding protein mRNA in the liver and soleus muscle and the expression of the uncoupling protein 3 (UCP3) mRNA in the heart, soleus muscle, and mesenteric fat, but not in the brown adipose tissue. Furthermore, NO-1886 did not affect UCP1 and UCP2 in brown adipose tissue. Therefore, amelioration of obesity by NO-1886 in OVX rats is possibly because of an the increased expression of fatty acid oxidation-related enzymes and UCP3, both of which are related to fatty acid transfer and fat use. Our study indicates that the LPL-promoting agent NO-1886 may be potentially beneficial in the treatment of obesity and obesity-linked health problems in postmenopausal women.
Kano
Seiichiro
S
Department of Pharmacology, Hokkaido College of Pharmacy, Hokkaido 047-0264, Japan.
Doi
Masako
M
D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D050612:Fatty Acid Transport Proteins / Q000096:biosynthesis / Q000235:genetics; D050556:Fatty Acid-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D007473:Ion Channels; D020738:Leptin / Q000097:blood; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009765:Obesity / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010052:Ovariectomy; D010101:Oxygen Consumption / Q000187:drug effects; D006180:Proton-Translocating ATPases / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071247:Uncoupling Protein 3
D001549:Benzamides; D001786:Blood Glucose; D002352:Carrier Proteins; D050612:Fatty Acid Transport Proteins; D050556:Fatty Acid-Binding Proteins; D000960:Hypolipidemic Agents; D007328:Insulin; D007473:Ion Channels; D020738:Leptin; D024101:Mitochondrial Proteins; D009943:Organophosphorus Compounds; D012333:RNA, Messenger; C000604394:Ucp3 protein, rat; D000071247:Uncoupling Protein 3; C082137:4-diethoxyphosphorylmethyl-N-(4-bromo-2-cyanophenyl)benzamide; D006180:Proton-Translocating ATPases