In @entity28 circulating @entity701 levels are not elevated, but high intraadipose @entity701 concentrations have been implicated. @entity11331 dehydrogenase type 1 (11HSD1) catalyzes the conversion of inactive @entity821 to active @entity701 , thus amplifying @entity4738 ( @entity4738 ) activation. In cohorts of @entity1 and @entity1 , we have shown increased ex vivo 11HSD1 activity in sc adipose tissue associated with in vivo @entity28 and insulin resistance. Using these biopsies, we have now validated this observation by measuring 11HSD1 and @entity4738 mRNA and examined the impact on intraadipose @entity701 concentrations, putative glucocorticoid regulated adipose target gene expression ( @entity2178 and leptin), and systemic measurements of @entity701 metabolism. From aliquots of sc adipose biopsies from 16 @entity1 and 16 @entity1 we extracted RNA for real-time PCR and @entity230 for immunoassays. Adipose 11HSD1 mRNA was closely related to 11HSD1 activity [standardized beta coefficient (SBC) = 0.58; P < 0.01], and both were positively correlated with parameters of @entity28 (e.g. for BMI, SBC = 0.48; P < 0.05 for activity, and SBC = 0.63; P < 0.01 for mRNA) and insulin sensitivity (log fasting plasma insulin; SBC = 0.44; P < 0.05 for activity, and SBC = 0.33; P = 0.09 for mRNA), but neither correlated with urinary @entity701 / @entity821 metabolite ratios. Adipose GR-alpha and @entity2178 mRNA levels were not associated with @entity28 or insulin resistance, but leptin mRNA was positively related to 11HSD1 activity (SBC = 0.59; P < 0.05) and tended to be associated with parameters of @entity28 (BMI: SBC = 0.40; P = 0.09), fasting insulin (SBC = 0.65; P < 0.05), and 11HSD1 mRNA (SBC = 0.40; P = 0.15). Intraadipose @entity701 (142 +/- 30 nmol/kg) was not related to 11HSD1 activity or expression, but was positively correlated with plasma @entity701 . These data confirm that @entity28 is associated with transcriptional up-regulation of 11HSD1 in adipose, which is not detected by conventional in vivo measurements of urinary @entity701 metabolites and is not accompanied by dysregulation of @entity4738 . Although this may drive a compensatory increase in leptin synthesis, whether it has an adverse effect on intraadipose @entity701 concentrations and GR-dependent gene regulation remains to be established.

Local and systemic impact of transcriptional up-regulation of @entity11331 dehydrogenase type 1 in adipose tissue in @entity1 XXXX .

@entity1 :: ('9606', 'Species') :: ['women', 'men'] @entity821 :: ('MESH:D003348', 'Chemical') :: ['cortisone'] @entity4738 :: ('2908', 'Gene') :: ['glucocorticoid receptor', 'GR'] @entity28 :: ('MESH:D009765', 'Disease') :: ['idiopathic obesity', 'obesity'] @entity2178 :: ('183', 'Gene') :: ['angiotensinogen'] @entity701 :: ('MESH:D006854', 'Chemical') :: ['cortisol'] @entity230 :: ('MESH:D013256', 'Chemical') :: ['steroids'] @entity11331 :: ('CHEBI:35346', 'Chemical') :: ['11beta-Hydroxysteroid']
@entity28 :: (MESH:D009765,Disease) :: ['obesity']
