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Overexpression of 11β-Hydroxysteroid Dehydrogenase-1 in Adipose Tissue Is Associated with Acquired Obesity and Features of Insulin Resistance: Studies in Young Adult Monozygotic Twins
Abstract
11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD-1) catalyzes the interconversion of inactive cortisone to active cortisol. Overexpression of 11beta-HSD-1 in murine adipose tissue results in glucocorticoid receptor (GR)alpha overexpression, central obesity, and insulin resistance. It is controversial whether 11beta-HSD-1 or GRalpha expression are increased in human adipose tissue in obesity. We studied effects of acquired obesity on 11beta-HSD-1 gene (real-time PCR) and protein (Western blotting) expression in sc adipose tissue in 17 monozygotic twin pairs aged 24-27 yr with a mean intrapair difference in body mass index (BMI) of 3.8 kg/m(2) (range 0.4-10.1 kg/m(2)). Intrapair correlations were calculated to study effects of acquired obesity on 11beta-HSD-1 expression. Western blot analysis of adipose tissue homogenates identified approximately 50- and approximately 68-kDa proteins specific for 11beta-HSD-1. Both structural forms correlated positively with 11beta-HSD-1 mRNA concentrations. Intrapair differences in 11beta-HSD-1 mRNA, and the 50- and 68-kDa proteins in sc adipose tissue correlated positively with those in BMI (kilograms per square meter) (r = 0.78 for 11beta-HSD-1 mRNA, P = 0.0002; r = 0.87 for the 11beta-HSD-1 50-kDa protein, P = 0.0003; and r = 0.62 for the 11beta-HSD-1 68-kDa protein, P = 0.033), total body fat (percent) (r = 0.65, P = 0.005; r = 0.83, P = 0.001; and r = 0.69, P = 0.013, respectively) and sc fat (cubed centimeters) (r = 0.66, P = 0.004; r = 0.94, P = 0.0001; and r = 0.71, P = 0.009, respectively). Furthermore, 11beta-HSD-1 mRNA and 50-kDa protein expression, but not 68-kDa protein expression, correlated positively with intrapair differences in intraabdominal fat mass (cubed centimeters) (r = 0.62, P = 0.008; r = 0.69, P = 0.013; r = 0.48, P = 0.112) and serum fasting insulin concentration (milliunits per liter) (r = 0.76, P = 0.0004; r = 0.60, P = 0.037; and r = 0.43, P = 0.160, respectively). Intrapair differences in GRalpha expression were significantly inversely correlated with those in BMI and total and sc fat mass. In conclusion, expression of 11beta-HSD-1 in sc adipose tissue is increased in human acquired obesity and is closely related to accumulation of sc and intraabdominal fat and features of insulin resistance.
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“These include increased production of inflammatory cytokines, 35,36 plasminogen activator inhibitor-1, 37 and other bioactive products 38 -40 ; at the same time the potentially protective adipokine, adiponectin, is reduced.41,42”
From Diagnosis and Management of the Metabolic Syndrome: An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement (2005) · cites this paper as [39]
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Metadata
- Authors
- Kannisto, K., Pietiläinen, K. H., Ehrenborg, E., Rissanen, A., Kaprio, J., Hamsten, A., & Yki-Järvinen, H.
- Affiliations
- Karolinska Institutet (SE)
- University of Helsinki (FI)
- Helsinki University Hospital (FI)
- Corresponding author
- Kannisto, Katja
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2004-09
- Volume
- 89
- Issue
- 9
- Pages
- 4414-4421
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2102335700
- Cited by
- 205
- References
- 45
- Citations by year
- 2026: 2 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 4 · 2020: 1 · 2019: 3 · 2018: 2 · 2017: 6 · 2016: 5 · 2015: 8 · 2014: 11 · 2013: 10 · 2012: 10
- FWCI
- 17.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Helsingin ja Uudenmaan Sairaanhoitopiiri
- European Commission (QLG2-CT-2002-01254, 01254)
- Hjärt-Lungfonden
- Karolinska Institutet
- Stockholms Läns Landsting
- Svenska Läkaresällskapet
- Medical Research Council
- Socialstyrelsen
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- 11β-hydroxysteroid dehydrogenase type 1, insulin resistance, subcutaneous adipose tissue, monozygotic twins, glucocorticoid receptor alpha, cortisol, body mass index, adipose tissue gene expression, young adults, adipocyte hypertrophy
- MeSH terms
- Adipose Tissue, Fatty Acids, Nonesterified, Humans, Insulin Resistance, Obesity, Receptors, Glucocorticoid, RNA, Messenger, Twins, Monozygotic, Up-Regulation, Gene Expression Regulation, Enzymologic, 11-beta-Hydroxysteroid Dehydrogenase Type 1
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