Reversal of visceral adiposity in candy-diet fed female Wistar rats by the CB1 receptor antagonist rimonabant

被引:19
作者
Herling, A. W. [1 ]
Kilp, S. [1 ]
Juretschke, H-P [1 ]
Neumann-Haefelin, C. [1 ]
Gerl, M. [1 ]
Kramer, W. [1 ]
机构
[1] Sanofi Aventis Deutschland GmbH, Therapeut Dept Metab, Pharmacol, D-65926 Frankfurt, Germany
关键词
body fat; fat distribution; ectopic lipid accumulation; in vivo MRS/MRI; fatty acid metabolism; metabolic syndrome;
D O I
10.1038/ijo.2008.105
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: The severity of obesity is often more determined by the distribution of fat depots rather than by body weight itself. Therefore, the effect of rimonabant on fat distribution pattern was investigated in female candy-fed Wistar rats. Design: Female Wistar rats were fed a high fat, high carbohydrate (candy-) diet for 12 weeks. During the last 6 weeks rats were treated with rimonabant. Food intake and body weight development were investigated, as well as effects on total body fat, especially visceral fat and ectopic lipid accumulation in skeletal muscle and liver, determined by in vivo magnetic resonance imaging/magnetic resonance spectroscopy. Results: Candy-diet increased body weight, which was predominantly due to the increased total fat mass with predominance of visceral fat accumulation. Treatment with rimonabant fully reversed the weight gain and fat deposition in the visceral cavity and skeletal muscle, in contrast to pair feeding. In spite of an only transient reduction of food intake, body weight reduction, as well as normalized body fat, reduced visceral fat and intramyocellular lipids were maintained over the treatment period. Conclusions: We conclude that additional factors other than reduced caloric intake must be responsible for the improvements in these lipid parameters. The complete cluster of results is consistent with increased lipid oxidation caused by rimonabant.
引用
收藏
页码:1363 / 1372
页数:10
相关论文
共 39 条
[1]   Regional adipocity in man [J].
Arner, P .
JOURNAL OF ENDOCRINOLOGY, 1997, 155 (02) :191-192
[2]   Is rimonabant a safe and effective treatment for obesity? [J].
Aronne, Louis J. .
NATURE CLINICAL PRACTICE ENDOCRINOLOGY & METABOLISM, 2007, 3 (05) :388-389
[3]  
BEHA A, 2006, AM J PHYSIOL-ENDOC M, pE989
[4]   The cannabinoid CB1 receptor antagonist SR141716 increases Acrp30 mRNA expression in adipose tissue of obese fa/fa rats and in cultured adipocyte cells [J].
Bensaid, M ;
Gary-Bobo, M ;
Esclangon, A ;
Maffrand, JP ;
Le Fur, G ;
Oury-Donat, F ;
Soubrié, P .
MOLECULAR PHARMACOLOGY, 2003, 63 (04) :908-914
[5]  
Bergmeyer H.U., 1974, METHODEN ENZYMATISCH
[6]   The obesity pipeline: current strategies in the development of anti-obesity drugs [J].
Cooke, Dunstan ;
Bloom, Steve .
NATURE REVIEWS DRUG DISCOVERY, 2006, 5 (11) :919-931
[7]   Abdominal obesity and metabolic syndrome [J].
Despres, Jean-Pierre ;
Lemieux, Isabelle .
NATURE, 2006, 444 (7121) :881-887
[8]   Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia [J].
Despres, JP ;
Golay, A ;
Sjostrom, L .
NEW ENGLAND JOURNAL OF MEDICINE, 2005, 353 (20) :2121-2134
[9]   REGIONAL DISTRIBUTION OF BODY-FAT, PLASMA-LIPOPROTEINS, AND CARDIOVASCULAR-DISEASE [J].
DESPRES, JP ;
MOORJANI, S ;
LUPIEN, PJ ;
TREMBLAY, A ;
NADEAU, A ;
BOUCHARD, C .
ARTERIOSCLEROSIS, 1990, 10 (04) :497-511
[10]   Role of early plasma membrane events in chemotherapy-induced cell death [J].
Dimanche-Boitrel, MT ;
Meurette, O ;
Rebillard, A ;
Lacour, S .
DRUG RESISTANCE UPDATES, 2005, 8 (1-2) :5-14