Depot-specific modulation of rat intraabdominal adipose tissue lipid metabolism by pharmacological inhibition of 11beta-hydroxysteroid dehydrogenase type 1

Endocrinology. 2007 May;148(5):2391-7. doi: 10.1210/en.2006-1199. Epub 2007 Feb 1.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / antagonists & inhibitors*
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / metabolism
  • Abdominal Fat / enzymology*
  • Animals
  • Carnitine O-Palmitoyltransferase / genetics
  • Carnitine O-Palmitoyltransferase / metabolism
  • Diacylglycerol O-Acyltransferase / genetics
  • Dietary Sucrose / pharmacology
  • Disease Models, Animal
  • Enzyme Inhibitors / pharmacology*
  • Gene Expression Regulation, Enzymologic
  • Lipid Metabolism / drug effects*
  • Lipid Metabolism / physiology
  • Lipolysis / physiology
  • Male
  • Obesity / drug therapy*
  • Obesity / metabolism
  • Phosphoenolpyruvate Carboxykinase (GTP) / genetics
  • Phospholipases A / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Stearoyl-CoA Desaturase / genetics
  • fas Receptor / genetics


  • Dietary Sucrose
  • Enzyme Inhibitors
  • Fas protein, mouse
  • RNA, Messenger
  • fas Receptor
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1
  • Stearoyl-CoA Desaturase
  • Dgat1 protein, rat
  • Diacylglycerol O-Acyltransferase
  • Carnitine O-Palmitoyltransferase
  • Phospholipases A
  • Phosphoenolpyruvate Carboxykinase (GTP)