Up-Regulation of mRNA Levels of 11β-Hydroxysteroid Dehydrogenase Type 1 in the Liver of Morbidly Obese Patients with Metabolic Syndrome

2011 ◽  
pp. P2-583-P2-583
Author(s):  
Esther Torrecilla-Garcia ◽  
Gumersindo Fernandez-Vazquez ◽  
David Vicent-Lopez ◽  
Franco Sanchez-Franco ◽  
Lucio Cabrerizo-Garcia ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Hydroxysteroid Dehydrogenase ◽  
Morbidly Obese ◽  
Mrna Levels ◽  
Obese Patients

Overexpression of hepatic 5α-reductase and 11β-hydroxysteroid dehydrogenase type 1 in visceral adipose tissue is associated with hyperinsulinemia in morbidly obese patients

Metabolism ◽  
2011 ◽  
Vol 60 (12) ◽  
pp. 1775-1780 ◽  
Author(s):  
René Baudrand ◽  
José Miguel Domínguez ◽  
Cristian A. Carvajal ◽  
Arnoldo Riquelme ◽  
Carmen Campino ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
Hydroxysteroid Dehydrogenase ◽  
Morbidly Obese ◽  
Obese Patients ◽  
Visceral Adipose

11β-Hydroxysteroid Dehydrogenase Type 1 is Overexpressed in Subcutaneous Adipose Tissue of Morbidly Obese Patients

2008 ◽  
Vol 19 (6) ◽  
pp. 764-770 ◽  
Author(s):  
Rodrigo Muñoz ◽  
Cristian Carvajal ◽  
Alex Escalona ◽  
Camilo Boza ◽  
Gustavo Pérez ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Hydroxysteroid Dehydrogenase ◽  
Morbidly Obese ◽  
Obese Patients ◽  
Subcutaneous Adipose

scholarly journals Proinflammatory Cytokine Induction of 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD1) in Human Adipocytes Is Mediated by MEK, C/EBPβ, and NF-κB/RelA

2014 ◽  
Vol 99 (1) ◽  
pp. E160-E168 ◽  
Author(s):  
Cristina L. Esteves ◽  
Val Kelly ◽  
Amandine Breton ◽  
Ashley I. Taylor ◽  
Christopher C. West ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Acetylsalicylic Acid ◽  
Proinflammatory Cytokines ◽  
Hydroxysteroid Dehydrogenase ◽  
Low Grade ◽  
Mrna Levels ◽  
Human Adipocytes ◽  
Cytokine Induction

Context: Levels of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which regenerates active glucocorticoids, are selectively elevated in adipose tissue in human obesity and metabolic syndrome, both conditions associated with chronic low-grade inflammation. 11β-HSD1 expression is induced by proinflammatory cytokines in a variety of cell types, including in human adipocytes differentiated in vitro. Objective: Our objective was to determine the mechanisms by which proinflammatory cytokines induce 11β-HSD1 in human adipocytes. Results: The proinflammatory cytokines IL-1α (10 ng/mL) and TNFα (20 ng/mL) increased 11β-HSD1 mRNA levels in human primary adipocyte fractions and Simpson-Golabi-Behmel syndrome (SGBS) adipocytes (P < .001). Inhibition of the MAPK/ERK kinase (MEK) attenuated CCAAT/enhancer binding protein (C/EBP) β phosphorylation at Thr235 and IL-1α/TNFα induction of 11β-HSD1 (P ≤ .007). The small interfering RNA-mediated knockdown of C/EBPβ and nuclear factor (NF)-κB/RelA or inhibition of NF-κB/RelA also attenuated cytokine induction of 11β-HSD1 (P ≤ .001). Moreover, induction of 11β-HSD1 by IL-1α in SGBS cells was associated with nuclear localization of C/EBPβ and NF-κB/RelA. Chromatin immunoprecipitation experiments showed C/EBPβ and NF-κB/RelA located to the 11β-HSD1 promoter in human adipose tissue. Treatment of adipocyte fractions or SGBS adipocytes with metformin or acetylsalicylic acid, which target C/EBPβ and NF-κB/RelA signaling, attenuated the IL-1α induction of 11β-HSD1 (P ≤ .002). Conclusions: Increased proinflammatory signaling in inflamed adipose tissue may mediate elevated 11β-HSD1 expression at this site via MEK, C/EBPβ, and NF-κB/RelA. These molecules/signaling pathways are, therefore, potential targets for drugs, including metformin and acetylsalicylic acid, to prevent/decreased up-regulation of 11β-HSD1 in human obese/metabolic syndrome adipose tissue.

scholarly journals Tissue-specific dysregulation of 11β-hydroxysteroid dehydrogenase type 1 in overweight/obese women with polycystic ovary syndrome compared with weight-matched controls

2014 ◽  
Vol 171 (1) ◽  
pp. 47-57 ◽  
Author(s):  
Alessandra Gambineri ◽  
Flaminia Fanelli ◽  
Federica Tomassoni ◽  
Alessandra Munarini ◽  
Uberto Pagotto ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Hydroxysteroid Dehydrogenase ◽  
Whole Body ◽  
Mrna Levels ◽  
Ovary Syndrome ◽  
Tissue Specific ◽  
Cortisol Metabolism ◽  
Cortisol Metabolites

ContextAbnormal cortisol metabolism in polycystic ovary syndrome (PCOS) has been invoked as a cause of secondary activation of the hypothalamic–pituitary–adrenal axis and hence androgen excess. However, this is based on urinary excretion of cortisol metabolites, which cannot detect tissue-specific changes in metabolism and may be confounded by obesity.ObjectiveTo assess cortisol clearance and whole-body and tissue-specific activities of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1 (HSD11B1)) in PCOS.DesignCase–control study.SettingMedical center.PatientsA total of 20 overweight–obese unmedicated Caucasian women with PCOS, aged 18–45 years, and 20 Caucasian controls matched for age, BMI, body fat distribution, andHSD11B1genotypes (rs846910 and rs12086634).Main outcome measuresCortisol metabolites were measured in 24 h urine. During steady-state 9,11,12,12-[2H]4-cortisol infusion, cortisol clearance was calculated and whole-body HSD11B1 activity was assessed as the rate of appearance of 9,12,12-2H3-cortisol (d3-cortisol). Hepatic HSD11B1 activity was quantified as the generation of plasma cortisol following an oral dose of cortisone. Subcutaneous adipose HSD11B1 activity andHSD11B1mRNA were measured,ex vivo, in biopsies.ResultsUrinary cortisol metabolite excretion, deuterated cortisol clearance, and the rate of appearance of d3-cortisol did not differ between patients with PCOS and controls. However, hepatic HSD11B1 conversion of oral cortisone to cortisol was impaired (P<0.05), whereas subcutaneous abdominal adipose tissueHSD11B1mRNA levels and activity were increased (P<0.05) in women with PCOS when compared with controls.ConclusionsTissue-specific dysregulation of HSD11B1 is a feature of PCOS, over and above obesity, whereas increased clearance of cortisol may result from obesity rather than PCOS.

Altered corticosteroid metabolism differentially affects pituitary corticotropin response

2002 ◽  
Vol 282 (2) ◽  
pp. E466-E473 ◽  
Author(s):  
Junko Hanafusa ◽  
Tomoatsu Mune ◽  
Tetsuya Tanahashi ◽  
Yukinori Isomura ◽  
Tetsuya Suwa ◽  
...  
Keyword(s):  
Glycyrrhizic Acid ◽  
Mrna Level ◽  
Hydroxysteroid Dehydrogenase ◽  
Corticotropin Releasing Factor ◽  
Receptor Expression ◽  
Mrna Levels ◽  
Basal Plasma ◽  
Corticosterone Response ◽  
Pituitary Adrenal Axis

To evaluate the effects of altered corticosteroid metabolism on the hypothalamic-pituitary-adrenal axis, we examined rats treated with glycyrrhizic acid (G rats) or rifampicin (R rats) for 7 days. The half-life of exogenously administered hydrocortisone as a substitute for corticosterone was longer in G rats and shorter in R rats, with no differences in basal plasma levels of ACTH or corticosterone. The ACTH responses to human corticotropin-releasing factor (CRF) or insulin-induced hypoglycemia were greater in G rats and tended to be smaller in R rats compared with those in the control rats, whereas the corticosterone response was similar. No difference was observed in the content and mRNA level of hypothalamic CRF among the groups. The number and mRNA level of CRF receptor and type 1 11β-hydroxysteroid dehydrogenase (11-HSD1) mRNA level in the pituitary were increased in G rats but not changed in R rats, suggesting that chronically increased intrapituitary corticosterone upregulates pituitary CRF receptor expression. In contrast, CRF mRNA levels in the pituitary were increased in R rats. Our data indicate novel mechanisms of corticosteroid metabolic modulation and the involvement of pituitary 11-HSD1 and CRF in glucocorticoid feedback physiology.

Sign in / Sign up

Export Citation Format

Share Document