DNA microarray analysis of white adipose tissue from obese (fa/fa) Zucker rats treated with a β3-adrenoceptor agonist, KTO-7924

被引:12
作者
Oana, F [1 ]
Homma, T [1 ]
Takeda, H [1 ]
Matsuzawa, A [1 ]
Akahane, S [1 ]
Isaji, M [1 ]
Akahane, M [1 ]
机构
[1] Kissei Pharmaceut Co Ltd, Div Discovery Res, Nagano 3998304, Japan
关键词
microarray; beta 3-adrenergic receptor; obesity; lipid oxidation; rat;
D O I
10.1016/j.phrs.2005.05.014
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
We aimed to examine the effects of KTO-7924 (beta 3-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 beta(3)-adrenoceptors by KTO-7924 causes BAT-like adipocytes to appear in RP WAT, and improves lipid metabolism. (c) 2005 Elsevier Ltd. All rights reserved.
引用
收藏
页码:395 / 400
页数:6
相关论文
共 27 条
[1]   Leptin signaling [J].
Ahima, RS ;
Osei, SY .
PHYSIOLOGY & BEHAVIOR, 2004, 81 (02) :223-241
[2]  
Akahane S, 2004, DIABETOLOGIA, V47, pA256
[3]   β3-adrenoceptor agonists:: potential, pitfalls and progress [J].
Arch, JRS .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2002, 440 (2-3) :99-107
[4]   Brown adipose tissue: Function and physiological significance [J].
Cannon, B ;
Nedergaard, J .
PHYSIOLOGICAL REVIEWS, 2004, 84 (01) :277-359
[5]   Phenotypes of mouse diabetes and rat fatty due to mutations in the OB (leptin) receptor [J].
Chua, SC ;
Chung, WK ;
WuPeng, XS ;
Zhang, YY ;
Liu, SM ;
Tartaglia, L ;
Leibel, RL .
SCIENCE, 1996, 271 (5251) :994-996
[6]  
Chung K Fan, 2004, Treat Respir Med, V3, P279, DOI 10.2165/00151829-200403050-00002
[7]   GENETIC-VARIATION IN THE BETA(3)-ADRENERGIC RECEPTOR AND AN INCREASED CAPACITY TO GAIN WEIGHT IN PATIENTS WITH MORBID-OBESITY [J].
CLEMENT, K ;
VAISSE, C ;
MANNING, BS ;
BASDEVANT, A ;
GUYGRAND, B ;
RUIZ, J ;
SILVER, KD ;
SHULDINER, AR ;
FROGUEL, P ;
STROSBERG, AD .
NEW ENGLAND JOURNAL OF MEDICINE, 1995, 333 (06) :352-354
[8]  
COUSIN B, 1992, J CELL SCI, V103, P931
[9]   Beta3-adrenoceptor agonists as anti-diabetic and anti-obesity drugs in humans [J].
de Souza, CJ ;
Burkey, BF .
CURRENT PHARMACEUTICAL DESIGN, 2001, 7 (14) :1433-1449
[10]   The adipocyte:: a model for integration of endocrine and metabolic signaling in energy metabolism regulation [J].
Frühbeck, G ;
Gómez-Ambrosi, J ;
Muruzábal, FJ ;
Burrell, MA .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2001, 280 (06) :E827-E847