Depot-Specific Modulation of Rat Intraabdominal Adipose Tissue Lipid Metabolism by Pharmacological Inhibition of 11β-Hydroxysteroid Dehydrogenase Type 1

The metabolic consequences of visceral obesity have been associated with amplification of glucocorticoid action by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in adipose tissue. This study aimed to assess in a rat model of diet-induced obesity the effects of pharmacological 11β-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 11β-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 enz...