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The Journal of Clinical Endocrinology & Metabolism Vol. 89, No. 9 4414-4421
Copyright © 2004 by The Endocrine Society

Overexpression of 11ß-Hydroxysteroid Dehydrogenase-1 in Adipose Tissue Is Associated with Acquired Obesity and Features of Insulin Resistance: Studies in Young Adult Monozygotic Twins

Katja Kannisto, Kirsi H. Pietiläinen, Ewa Ehrenborg, Aila Rissanen, Jaakko Kaprio, Anders Hamsten and Hannele Yki-Järvinen

Department of Medicine (K.K., E.E., A.H., H.Y.-J.), Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Institutet, S-17176 Stockholm, Sweden; Finnish Twin Cohort Study (K.H.P., J.K.), Department of Public Health, University of Helsinki, 00014 Helsinki, Finland; Obesity Research Unit (K.H.P., A.R.), Department of Psychiatry, Helsinki University Hospital, 00029 Helsinki, Finland; Department of Medicine (K.H.P., H.Y.-J.), Division of Diabetes, Helsinki University Central Hospital, 00029 Helsinki, Finland; and National Public Health Institute (J.K.), Department of Mental Health and Alcohol Research, 00300 Helsinki, Finland

Address all correspondence and requests for reprints to: Katja Kannisto, Department of Medicine, Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Institutet, S-17176 Stockholm, Sweden. E-mail: katja.kannisto{at}medks.ki.se.

11ß-Hydroxysteroid dehydrogenase type 1 (11ß-HSD-1) catalyzes the interconversion of inactive cortisone to active cortisol. Overexpression of 11ß-HSD-1 in murine adipose tissue results in glucocorticoid receptor (GR){alpha} overexpression, central obesity, and insulin resistance. It is controversial whether 11ß-HSD-1 or GR{alpha} expression are increased in human adipose tissue in obesity. We studied effects of acquired obesity on 11ß-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/m2 (range 0.4–10.1 kg/m2). Intrapair correlations were calculated to study effects of acquired obesity on 11ß-HSD-1 expression. Western blot analysis of adipose tissue homogenates identified approximately 50- and approximately 68-kDa proteins specific for 11ß-HSD-1. Both structural forms correlated positively with 11ß-HSD-1 mRNA concentrations. Intrapair differences in 11ß-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 11ß-HSD-1 mRNA, P = 0.0002; r = 0.87 for the 11ß-HSD-1 50-kDa protein, P = 0.0003; and r = 0.62 for the 11ß-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, 11ß-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 GR{alpha} expression were significantly inversely correlated with those in BMI and total and sc fat mass.

In conclusion, expression of 11ß-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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