Abstract
BackgroundThe enzyme 11-beta hydroxysteroid dehydrogenase type 1 (HSD11B1) converts inactive cortisone to active cortisol in a process mediated by the enzyme hexose-6-phosphate dehydrogenase (H6PD). The generation of cortisol from this reaction may increase intra-abdominal cortisol levels and contribute to the physiopathogenesis of obesity and metabolic syndrome (MetS). The relationship of HSD11B1 rs45487298 and H6PD rs6688832 polymorphisms with obesity and MetS was studied. We also studied how HSD11B1 abdominal subcutaneous (SAT) and visceral adipose tissue (VAT) gene expression is related to body fat distribution.MethodsRates of obesity and MetS features were cross-sectionally analyzed according to these polymorphisms in 1006 Brazilian white patients with type 2 diabetes (T2DM). Additionally, HSD11B1 expression was analyzed in VAT and SAT in a different cohort of 28 participants with and without obesity who underwent elective abdominal operations.ResultsAlthough polymorphisms of the two genes were not individually associated with MetS features, a synergistic effect was observed between both. Carriers of at least three minor alleles exhibited lower BMI compared to those with two or fewer minor alleles adjusting for gender and age (27.4 ± 4.9 vs. 29.3 ± 5.3 kg/m2; P = 0.005; mean ± SD). Obesity frequency was also lower in the first group (24.4% vs. 41.6%, OR = 0.43, 95% CI 0.21–0.87; P = 0.019). In the second cohort of 28 subjects, HSD11B1 gene expression in VAT was inversely correlated with BMI (r = − 0.435, P = 0.034), waist circumference (r = − 0.584, P = 0.003) and waist-to-height ratio (r = − 0.526, P = 0.010).ConclusionsThese polymorphisms might interact in the protection against obesity in T2DM individuals. Obese individuals may have decreased intra-abdominal VAT HSD11B1 gene expression resulting in decreasing intra-abdominal cortisol levels as a compensatory mechanism against central and general adiposity.
Highlights
The enzyme 11-beta hydroxysteroid dehydrogenase type 1 (HSD11B1) converts inactive cortisone to active cortisol in a process mediated by the enzyme hexose-6-phosphate dehydrogenase (H6PD)
We investigated the relationship of 11-beta hydrosteroid dehydrogenase type 1 (HSD11B1) gene expression in abdominal subcutaneous (SAT) and visceral (VAT) adipose tissue with body fat distribution in individuals with and without metabolic syndrome (MetS)
Of the 998 individuals genotyped for the HSD11B1 rs45487298:delA>insA polymorphism, 654 (65.5%) individuals were homozygous for the delA allele, 311 (31.2%) were heterozygous, and 33 (3.3%) were homozygous for the insA allele
Summary
The enzyme 11-beta hydroxysteroid dehydrogenase type 1 (HSD11B1) converts inactive cortisone to active cortisol in a process mediated by the enzyme hexose-6-phosphate dehydrogenase (H6PD). Weight gain promotes body fat accumulation, resulting in the activation of the inflammatory pathways, abnormal fat metabolism and the development of insulin resistance [5, 6] The mechanisms behind this process are not clear, but in view of the similarities between individuals with Cushing’s syndrome and those with metabolic syndrome (MetS), it has been proposed that, despite normal levels of circulating cortisol, these phenotypes might arise as a consequence of tissue-specific cortisol excess due to increased activity of the enzyme 11-beta hydroxysteroid dehydrogenase type 1 (HSD11B1) [7]. HSD11B1 is a bidirectional enzyme in vitro, under normal circumstances it works as a reductase in the liver and adipose tissue, catalyzing the conversion of hormonally inactive cortisone into its active form, cortisol [8] The activity of this enzyme is dependent on the provision of NADPH by the co-localized enzyme hexose6-phosphate dehydrogenase (H6PD). In the absence of H6PD, HSD11B1 acts as a dehydrogenase, inactivating cortisol [9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
