Interaction of HSD11B1 and H6PD polymorphisms in subjects with type 2 diabetes are protective factors against obesity: a cross-sectional study
Abstract Background 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). The generation of cortisol from this reaction may increase intra-abdominal cortisol levels...
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| Format: | Article |
| Language: | English |
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BMC
2019-09-01
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| Series: | Diabetology & Metabolic Syndrome |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13098-019-0474-2 |
| _version_ | 1818340442818740224 |
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| author | Marcio F. Chedid Filipe V. do Nascimento Fernanda S. de Oliveira Bianca M. de Souza Cleber R. P. Kruel Richard R. Gurski Luis H. Canani Daisy Crispim Fernando Gerchman |
| author_facet | Marcio F. Chedid Filipe V. do Nascimento Fernanda S. de Oliveira Bianca M. de Souza Cleber R. P. Kruel Richard R. Gurski Luis H. Canani Daisy Crispim Fernando Gerchman |
| author_sort | Marcio F. Chedid |
| collection | DOAJ |
| description | Abstract Background 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). 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. Methods Rates 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. Results Although 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). Conclusions These 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. |
| first_indexed | 2024-12-13T15:42:58Z |
| format | Article |
| id | doaj.art-8b7037198cf74c6889a0128a78b1431b |
| institution | Directory Open Access Journal |
| issn | 1758-5996 |
| language | English |
| last_indexed | 2024-12-13T15:42:58Z |
| publishDate | 2019-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Diabetology & Metabolic Syndrome |
| spelling | doaj.art-8b7037198cf74c6889a0128a78b1431b2022-12-21T23:39:46ZengBMCDiabetology & Metabolic Syndrome1758-59962019-09-0111111010.1186/s13098-019-0474-2Interaction of HSD11B1 and H6PD polymorphisms in subjects with type 2 diabetes are protective factors against obesity: a cross-sectional studyMarcio F. Chedid0Filipe V. do Nascimento1Fernanda S. de Oliveira2Bianca M. de Souza3Cleber R. P. Kruel4Richard R. Gurski5Luis H. Canani6Daisy Crispim7Fernando Gerchman8Postgraduate Program of Surgical Sciences, Universidade Federal do Rio Grande do SulPostgraduate Program in Medical Science: Endocrinology, Universidade Federal do Rio Grande do Sul (UFRGS)Postgraduate Program in Medical Science: Endocrinology, Universidade Federal do Rio Grande do Sul (UFRGS)Postgraduate Program of Surgical Sciences, Universidade Federal do Rio Grande do SulPostgraduate Program of Surgical Sciences, Universidade Federal do Rio Grande do SulPostgraduate Program of Surgical Sciences, Universidade Federal do Rio Grande do SulPostgraduate Program in Medical Science: Endocrinology, Universidade Federal do Rio Grande do Sul (UFRGS)Postgraduate Program in Medical Science: Endocrinology, Universidade Federal do Rio Grande do Sul (UFRGS)Postgraduate Program in Medical Science: Endocrinology, Universidade Federal do Rio Grande do Sul (UFRGS)Abstract Background 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). 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. Methods Rates 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. Results Although 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). Conclusions These 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.http://link.springer.com/article/10.1186/s13098-019-0474-2Gene expressionCortisol11-beta hydroxysteroid dehydrogenase type 1Hexose-6-phosphate dehydrogenaseVisceralAdipose tissue |
| spellingShingle | Marcio F. Chedid Filipe V. do Nascimento Fernanda S. de Oliveira Bianca M. de Souza Cleber R. P. Kruel Richard R. Gurski Luis H. Canani Daisy Crispim Fernando Gerchman Interaction of HSD11B1 and H6PD polymorphisms in subjects with type 2 diabetes are protective factors against obesity: a cross-sectional study Diabetology & Metabolic Syndrome Gene expression Cortisol 11-beta hydroxysteroid dehydrogenase type 1 Hexose-6-phosphate dehydrogenase Visceral Adipose tissue |
| title | Interaction of HSD11B1 and H6PD polymorphisms in subjects with type 2 diabetes are protective factors against obesity: a cross-sectional study |
| title_full | Interaction of HSD11B1 and H6PD polymorphisms in subjects with type 2 diabetes are protective factors against obesity: a cross-sectional study |
| title_fullStr | Interaction of HSD11B1 and H6PD polymorphisms in subjects with type 2 diabetes are protective factors against obesity: a cross-sectional study |
| title_full_unstemmed | Interaction of HSD11B1 and H6PD polymorphisms in subjects with type 2 diabetes are protective factors against obesity: a cross-sectional study |
| title_short | Interaction of HSD11B1 and H6PD polymorphisms in subjects with type 2 diabetes are protective factors against obesity: a cross-sectional study |
| title_sort | interaction of hsd11b1 and h6pd polymorphisms in subjects with type 2 diabetes are protective factors against obesity a cross sectional study |
| topic | Gene expression Cortisol 11-beta hydroxysteroid dehydrogenase type 1 Hexose-6-phosphate dehydrogenase Visceral Adipose tissue |
| url | http://link.springer.com/article/10.1186/s13098-019-0474-2 |
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