DNA microarray analysis of white adipose tissue from obese (fa/fa) Zucker rats treated with a beta3-adrenoceptor agonist, KTO-7924

Pharmacol Res. 2005 Nov;52(5):395-400. doi: 10.1016/j.phrs.2005.05.014. Epub 2005 Jul 18.

Abstract

We aimed to examine the effects of KTO-7924 (beta3-adrenoceptor agonist) on lipid metabolism and mRNA expressions in retroperitoneal white adipose tissue (RP WAT) in obese (fa/fa) Zucker rats using DNA microarray. Oral KTO-7924 for 28 days significantly decreased RP WAT weight, plasma triglyceride, free fatty acid, and insulin, and improved insulin resistance in oral glucose tolerance tests. In RP WAT of KTO-7924-treated rats, DNA microarray analysis revealed specifically enhanced mRNA expressions of uncoupling protein 1 (UCP1) and cytochrome c oxidase subunit VIII-H (COX8H), which are reportedly highly expressed in brown adipose tissue (BAT). Since these mRNA expression levels in RP WAT were significantly lower in obese (fa/fa) Zucker rats than in lean Zucker rats, these genes may be important in lipid metabolism. Our results imply that in obese (fa/fa) Zucker rats, continuous stimulation of beta3-adrenoceptors by KTO-7924 causes BAT-like adipocytes to appear in RP WAT, and improves lipid metabolism.

MeSH terms

  • Adipose Tissue / metabolism*
  • Adipose Tissue, Brown / metabolism
  • Adrenergic Agonists / pharmacology*
  • Adrenergic beta-3 Receptor Agonists*
  • Animals
  • Gene Expression Profiling
  • Insulin Resistance
  • Lipid Metabolism / drug effects
  • Male
  • Obesity / metabolism*
  • Oligonucleotide Array Sequence Analysis*
  • Rats
  • Rats, Zucker

Substances

  • Adrenergic Agonists
  • Adrenergic beta-3 Receptor Agonists