NO-1886 (ibrolipim), a lipoprotein lipase-promoting agent, accelerates the expression of UCP3 messenger RNA and ameliorates obesity in ovariectomized rats

Metabolism. 2006 Feb;55(2):151-8. doi: 10.1016/j.metabol.2005.08.007.

Abstract

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.

MeSH terms

  • Adipose Tissue, Brown / drug effects
  • Adipose Tissue, Brown / metabolism
  • Animals
  • Benzamides / pharmacology*
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Body Weight / drug effects
  • Carrier Proteins / biosynthesis*
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Eating / drug effects
  • Fatty Acid Transport Proteins / biosynthesis
  • Fatty Acid Transport Proteins / genetics
  • Fatty Acid-Binding Proteins / biosynthesis
  • Fatty Acid-Binding Proteins / genetics
  • Female
  • Gene Expression / drug effects
  • Hypolipidemic Agents / pharmacology*
  • Insulin / blood
  • Ion Channels
  • Leptin / blood
  • Mitochondrial Proteins
  • Muscle, Skeletal / metabolism
  • Myocardium / metabolism
  • Obesity / blood
  • Obesity / drug therapy*
  • Obesity / metabolism*
  • Organophosphorus Compounds / pharmacology*
  • Ovariectomy
  • Oxygen Consumption / drug effects
  • Proton-Translocating ATPases / biosynthesis
  • Proton-Translocating ATPases / genetics
  • RNA, Messenger / biosynthesis*
  • RNA, Messenger / chemistry
  • RNA, Messenger / genetics
  • Random Allocation
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Uncoupling Protein 3

Substances

  • Benzamides
  • Blood Glucose
  • Carrier Proteins
  • Fatty Acid Transport Proteins
  • Fatty Acid-Binding Proteins
  • Hypolipidemic Agents
  • Insulin
  • Ion Channels
  • Leptin
  • Mitochondrial Proteins
  • Organophosphorus Compounds
  • RNA, Messenger
  • Ucp3 protein, rat
  • Uncoupling Protein 3
  • 4-diethoxyphosphorylmethyl-N-(4-bromo-2-cyanophenyl)benzamide
  • Proton-Translocating ATPases