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

@article{citeulike:1333658, abstract = {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 11{beta}-hydroxysteroid dehydrogenase type 1 (11{beta}-HSD-1) found in adipose tissue of obese humans and rodents underlies the phenotypic similarities between idiopathic and "Cushingoid" obesity. Transgenic overexpression of 11{beta}-HSD-1 in adipose tissue reproduces a metabolic syndrome in mice, whereas 11{beta}-HSD-1 deficiency or inhibition has beneficial metabolic effects, at least on liver metabolism. Here we report novel protective effects of 11{beta}-HSD-1 deficiency on adipose function, distribution, and gene expression in vivo in 11{beta}-HSD-1 nullizygous (11{beta}-HSD-1-/-) mice. 11{beta}-HSD-1-/- mice expressed lower resistin and tumor necrosis factor-{alpha}, but higher peroxisome proliferator-activated receptor-{gamma}, adiponectin, and uncoupling protein-2 mRNA levels in adipose, indicating insulin sensitization. Isolated 11{beta}-HSD-1-/- adipocytes exhibited higher basal and insulin-stimulated glucose uptake. 11{beta}-HSD-1-/- mice also exhibited reduced visceral fat accumulation upon high-fat feeding. High-fat-fed 11{beta}-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 11{beta}-HSD-1 deficiency beneficially alters adipose tissue distribution and function, complementing the reported effects of hepatic 11{beta}-HSD-1 deficiency or inhibition. 10.2337/diabetes.53.4.931}, author = {Morton, Nicholas M. and Paterson, Janice M. and Masuzaki, Hiroaki and Holmes, Megan C. and Staels, Bart and Fievet, Catherine and Walker, Brian R. and Flier, Jeffrey S. and Mullins, John J. and Seckl, Jonathan R. }, citeulike-article-id = {1333658}, doi = {http://dx.doi.org/10.2337/diabetes.53.4.931}, journal = {Diabetes}, keywords = {11bhsd1, adipose, mouse, obesity}, month = {April}, number = {4}, pages = {931--938}, posted-at = {2007-05-25 21:08:23}, priority = {2}, title = {Novel Adipose Tissue-Mediated Resistance to Diet-Induced Visceral Obesity in 11{beta}-Hydroxysteroid Dehydrogenase Type 1-Deficient Mice}, url = {http://dx.doi.org/10.2337/diabetes.53.4.931}, volume = {53}, year = {2004} }

TY - JOUR ID - citeulike:1333658 L3 - citeulike-article-id:1333658 TI - Novel Adipose Tissue-Mediated Resistance to Diet-Induced Visceral Obesity in 11{beta}-Hydroxysteroid Dehydrogenase Type 1-Deficient Mice JF - Diabetes VL - 53 IS - 4 SP - 931 EP - 938 N2 - 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 11{beta}-hydroxysteroid dehydrogenase type 1 (11{beta}-HSD-1) found in adipose tissue of obese humans and rodents underlies the phenotypic similarities between idiopathic and "Cushingoid" obesity. Transgenic overexpression of 11{beta}-HSD-1 in adipose tissue reproduces a metabolic syndrome in mice, whereas 11{beta}-HSD-1 deficiency or inhibition has beneficial metabolic effects, at least on liver metabolism. Here we report novel protective effects of 11{beta}-HSD-1 deficiency on adipose function, distribution, and gene expression in vivo in 11{beta}-HSD-1 nullizygous (11{beta}-HSD-1-/-) mice. 11{beta}-HSD-1-/- mice expressed lower resistin and tumor necrosis factor-{alpha}, but higher peroxisome proliferator-activated receptor-{gamma}, adiponectin, and uncoupling protein-2 mRNA levels in adipose, indicating insulin sensitization. Isolated 11{beta}-HSD-1-/- adipocytes exhibited higher basal and insulin-stimulated glucose uptake. 11{beta}-HSD-1-/- mice also exhibited reduced visceral fat accumulation upon high-fat feeding. High-fat-fed 11{beta}-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 11{beta}-HSD-1 deficiency beneficially alters adipose tissue distribution and function, complementing the reported effects of hepatic 11{beta}-HSD-1 deficiency or inhibition. 10.2337/diabetes.53.4.931 KW - 11bhsd1 KW - adipose KW - mouse KW - obesity AU - Morton, Nicholas AU - Paterson, Janice AU - Masuzaki, Hiroaki AU - Holmes, Megan AU - Staels, Bart AU - Fievet, Catherine AU - Walker, Brian AU - Flier, Jeffrey AU - Mullins, John AU - Seckl, Jonathan PY - 2004/04/01/ UR - http://dx.doi.org/10.2337/diabetes.53.4.931 ER -