| Abstract | The metabolic consequences of visceral obesity have been associated with amplification of glucocorticoid action by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) in adipose tissue. This study aimed to assess in a rat model of diet-induced obesity the effects of pharmacological 11beta-HSD1 inhibition on the morphology and expression of key genes of lipid metabolism in intraabdominal adipose depots. Rats fed a high-sucrose, high-fat diet were treated or not with a specific 11beta-HSD1 inhibitor (compound A, 3 mg/kg.d) for 3 wk. Compound A did not alter food intake or body weight gain but specifically reduced mesenteric adipose weight (-18%) and adipocyte size, without significantly affecting those of epididymal or retroperitoneal depots. In mesenteric fat, the inhibitor decreased (to 25-50% of control) mRNA levels of genes involved in lipid synthesis (FAS, SCD1, DGAT1) and fatty acid cycling (lipolysis/reesterification, ATGL and PEPCK) and increased (30%) the activity of the fatty acid oxidation-promoting enzyme carnitine palmitoyltransferase 1. In striking contrast, in the epididymal depot, 11beta-HSD1 inhibition increased (1.5-5-fold) mRNA levels of those genes related to lipid synthesis/cycling and slightly decreased carnitine palmitoyltransferase 1 activity, whereas gene expression remained unaffected in the retroperitoneal depot. Compound A robustly reduced liver triacylglycerol content and plasma lipids. The study demonstrates that pharmacological inhibition of 11beta-HSD1, at a dose that does not alter food intake, reduces fat accretion specifically in the mesenterical adipose depot, exerts divergent intraabdominal depot-specific effects on genes of lipid metabolism, and reduces steatosis and lipemia. |
| Authors | Magalie Berthiaume, Mathieu Laplante, William Festuccia, Yves Gélinas, Sébastien Poulin, Josée Lalonde, Denis R Joanisse, Rolf Thieringer, Yves Deshaies
(Affiliation: Laval Hospital Research Center, Department of Anatomy and Physiology, Laval University, Quebec, Canada G1V 4G5.)
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| Journal | Endocrinology
(Endocrinology)
Vol. 148
Issue 5
Pg. 2391-7
(May 2007)
ISSN: 0013-7227 United States |
| PMID | 17272400
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Antigens, CD95
- Dietary Sucrose
- Enzyme Inhibitors
- Fas protein, mouse
- RNA, Messenger
- 11-beta-Hydroxysteroid Dehydrogenase Type 1
- Stearoyl-CoA Desaturase
- Dgat1 protein, rat
- Diacylglycerol O-Acyltransferase
- Carnitine O-Palmitoyltransferase
- Phospholipases A
- Phosphoenolpyruvate Carboxykinase (GTP)
|
| Topics |
- 11-beta-Hydroxysteroid Dehydrogenase Type 1
(antagonists & inhibitors, metabolism)
- Abdominal Fat
(enzymology)
- Animals
- Antigens, CD95
(genetics)
- Carnitine O-Palmitoyltransferase
(genetics, metabolism)
- Diacylglycerol O-Acyltransferase
(genetics)
- Dietary Sucrose
(pharmacology)
- Disease Models, Animal
- Enzyme Inhibitors
(pharmacology)
- Gene Expression Regulation, Enzymologic
- Lipid Metabolism
(drug effects, physiology)
- Lipolysis
(physiology)
- Male
- Obesity
(drug therapy, metabolism)
- Phosphoenolpyruvate Carboxykinase (GTP)
(genetics)
- Phospholipases A
(genetics)
- RNA, Messenger
(metabolism)
- Rats
- Rats, Sprague-Dawley
- Stearoyl-CoA Desaturase
(genetics)
|
