DNA microarray analysis of white adipose tissue from obese (fa/fa) Zucker rats treated with a beta3-adrenoceptor agonist, KTO-7924.
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.
Oana
Fumiki
F
Division of Discovery Research, Kissei Pharmaceutical Co. Ltd., 4365-1 Hotaka, Nagano 399-8304, Japan. fumiki_oana@pharm.kissei.co.jp
Homma
Toshiki
T
Takeda
Hiroo
H
Matsuzawa
Akane
A
Akahane
Satoshi
S
Isaji
Masayuki
M
Akahane
Masuo
M
D000273:Adipose Tissue / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000378:metabolism; D000322:Adrenergic Agonists / Q000494:pharmacology*; D058667:Adrenergic beta-3 Receptor Agonists; D000818:Animals; D020869:Gene Expression Profiling; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D009765:Obesity / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D011924:Rats, Zucker
D000322:Adrenergic Agonists; D058667:Adrenergic beta-3 Receptor Agonists