Overexpression of 11beta-hydroxysteroid dehydrogenase-1 in adipose tissue is associated with acquired obesity and features of insulin resistance: studies in young adult monozygotic twins.
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.
Kannisto
Katja
K
Department of Medicine, Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Institutet, S-17176 Stockholm, Sweden. katja.kannisto@medks.ki.se
Pietiläinen
Kirsi H
KH
Ehrenborg
Ewa
E
Rissanen
Aila
A
Kaprio
Jaakko
J
Hamsten
Anders
A
Yki-Järvinen
Hannele
H
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000032:analysis / Q000235:genetics*; D000273:Adipose Tissue / Q000201:enzymology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007333:Insulin Resistance; D009765:Obesity / Q000201:enzymology / Q000209:etiology*; D012333:RNA, Messenger / Q000032:analysis; D011965:Receptors, Glucocorticoid / Q000032:analysis; D014430:Twins, Monozygotic; D015854:Up-Regulation
D005230:Fatty Acids, Nonesterified; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; C411470:glucocorticoid receptor alpha; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1