PT - JOURNAL ARTICLE AU - Morton, Nicholas M. AU - Paterson, Janice M. AU - Masuzaki, Hiroaki AU - Holmes, Megan C. AU - Staels, Bart AU - Fievet, Catherine AU - Walker, Brian R. AU - Flier, Jeffrey S. AU - Mullins, John J. AU - Seckl, Jonathan R. TI - Novel Adipose Tissue–Mediated Resistance to Diet-Induced Visceral Obesity in 11β-Hydroxysteroid Dehydrogenase Type 1–Deficient Mice AID - 10.2337/diabetes.53.4.931 DP - 2004 Apr 01 TA - Diabetes PG - 931--938 VI - 53 IP - 4 4099 - http://diabetes.diabetesjournals.org/content/53/4/931.short 4100 - http://diabetes.diabetesjournals.org/content/53/4/931.full SO - Diabetes2004 Apr 01; 53 AB - The metabolic syndrome (visceral obesity, insulin resistance, 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 glucocorticoid reamplifying enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) found in adipose tissue of obese humans and rodents underlies the phenotypic similarities between idiopathic and “Cushingoid” obesity. Transgenic overexpression of 11β-HSD-1 in adipose tissue reproduces a metabolic syndrome in mice, whereas 11β-HSD-1 deficiency or inhibition has beneficial metabolic effects, at least on liver metabolism. Here we report novel protective effects of 11β-HSD-1 deficiency on adipose function, distribution, and gene expression in vivo in 11β-HSD-1 nullizygous (11β-HSD-1−/−) mice. 11β-HSD-1−/− mice expressed lower resistin and tumor necrosis factor-α, but higher peroxisome proliferator–activated receptor-γ, adiponectin, and uncoupling protein-2 mRNA levels in adipose, indicating insulin sensitization. Isolated 11β-HSD-1−/− adipocytes exhibited higher basal and insulin-stimulated glucose uptake. 11β-HSD-1−/− mice also exhibited reduced visceral fat accumulation upon high-fat feeding. High-fat–fed 11β-HSD-1−/− mice rederived onto the C57BL/6J strain resisted diabetes and weight gain despite consuming more calories. These data provide the first in vivo evidence that adipose 11β-HSD-1 deficiency beneficially alters adipose tissue distribution and function, complementing the reported effects of hepatic 11β-HSD-1 deficiency or inhibition.