Novel Adipose Tissue–Mediated Resistance to Diet-Induced Visceral Obesity in 11-Hydroxysteroid Dehydrogenase Type 1–Deficient Mice

tance, type 2 diabetes, and dyslipidemia) resembles Cushing’s Syndrome, but without elevated circulating glucocorticoid levels. An emerging concept suggests that the aberrantly elevated levels of the intracellular glu-cocorticoid reamplifying enzyme 11-hydroxysteroid dehydrogenase type 1 (11-HSD-1) found in adipose tissue of obese humans and rodents underlies the phe-notypic similarities between idiopathic and “Cushing-oid ” obesity. Transgenic overexpression of 11-HSD-1 in adipose tissue reproduces a metabolic syndrome in mice, whereas 11-HSD-1 deficiency or inhibition has beneficial metabolic effects, at least on liver metabo-lism. Here we report novel protective effects of 11-HSD-1 deficiency on adipose function, distribution, and gene expression in vivo in 11-HSD-1 nullizygous (11