Overexpression of 11β-Hydroxysteroid Dehydrogenase Type 1 in Hepatic and Visceral Adipose Tissue is Associated with Metabolic Disorders in Morbidly Obese Patients

Baudrand, René; Carvajal, Cristián A.; Riquelme, Arnoldo; Morales, Mauricio; Solı́s, Nancy; Pizarro, Margarita; Escalona, Alex; Boza, Camilo; Pérez, Gustavo; Domínguez, Angélica; Arrese, Marco; Fardella, Carlos E.

doi:10.1007/s11695-009-9937-0

Cited by 58 publications

(54 citation statements)

References 49 publications

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“…The results are conflicting when comparing HSD11B1 mRNA levels in the adipose tissue and liver of obese patients with or without MetS. In contrast to our results, Baudrand et al (13) did not find differences in HSD11B1 expression between obese subjects with and without MetS, while Torrecilla et al (35) observed higher mRNA levels of HSD11B1 in the liver of patients with MetS. Nevertheless, this particular finding of ours is in line with previous studies, in animal models and more particularly in transgenic mice, where overexpression of the HSD11B1 selectively in adipose tissue led to full MetS, with visceral obesity, hypertension, dyslipidaemia and IR (14).…”

Section: European Journal Of Endocrinologycontrasting

confidence: 99%

“…Independently of the MetS presence, the HSD11B1 mRNA levels were significantly higher in the liver than in SAT and VAT, a finding consistent with another study (13). This dominant expression of HSD11B1 in the liver may serve the important role of glucocorticoids in the regulation of gluconeogenic enzymes, hepatic glucose production and glycogen stores (27,28).…”

Section: Discussionsupporting

confidence: 88%

“…The enzyme HSD11B1 promotes the extra-adrenal production of cortisol by catalysing the regeneration from inactive cortisone and thus amplifying glucocorticoid action at the pre-receptor level. HSD11B1 is widely expressed throughout the body, mainly in the liver as well as in other tissues such as the visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) (9,10,11,12,13).…”

Section: Introductionmentioning

confidence: 99%

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Cortisol in tissue and systemic level as a contributing factor to the development of metabolic syndrome in severely obese patients

Constantinopoulos

Michalaki

Κοττόρου

et al. 2015

European Journal of Endocrinology

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Context: Adrenal and extra-adrenal cortisol production may be involved in the development of metabolic syndrome (MetS). Objective: To investigate the activity of the hypothalamic-pituitary-adrenal (HPA) axis and the expression of HSD11B1, nuclear receptor subfamily 3, group C, member 1 (glucocorticoid receptors) a (NR3C1a) and b (NR3C1b) in the liver, subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) of severely obese patients with and without MetS. Methods: The study included 37 severely obese patients (BMI R40 kg/m 2 ), 19 with MetS (MetSC group) and 18 without (MetSK group), studied before and during bariatric surgery. Before the day of surgery, urinary free cortisol (UFC) and diurnal variation of serum and salivary cortisol were estimated. During surgery, biopsies of the liver, VAT and SAT were obtained. The expression of HSD11B1, NR3C1a and NR3C1b was evaluated by RT-PCR.Results: UFC and area under the curve for 24-h profiles of serum and salivary cortisol were lower in the MetSK group. In the MetSK group, mRNA levels of HSD11B1 in liver exhibited a negative correlation with liver NR3C1a (LNR3C1a) and VAT expression of HSD11B1 was lower than the MetSC group. Conclusions: We observed a downregulation of the NR3C1a expression and lower VAT mRNA levels of HSD11B1 in the MetSK group, indicating a lower selective tissue cortisol production and action that could protect these patients from the metabolic consequences of obesity. In the MetSK group, a lower activity of the HPA axis was also detected. Taken together, cortisol in tissue and systematic level might play a role in the development of MetS in severely obese patients.

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Section: European Journal Of Endocrinologycontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cortisol in tissue and systemic level as a contributing factor to the development of metabolic syndrome in severely obese patients

Constantinopoulos

Michalaki

Κοττόρου

et al. 2015

European Journal of Endocrinology

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“…11b-HSD1 null mice exhibited decreased white adipose depot, resistance to hyperglycemia induced by fat feeding, and increased hepatic insulin sensitivity (Alberts et al 2002, 2003, Kershaw et al 2005, Stewart & Tomlinson 2009. By contrast, increased 11b-HSD1 activity in WAT resulted in the development of visceral adiposity, hyperglycemia, and insulin resistance in morbidly obese patients (Kannisto et al 2004, Baudrand et al 2010. Moreover, our previous studies suggested that 11b-HSD1 could promote differentiation of white adipocyte in vitro (Liu et al 2007).…”

Section: Discussionmentioning

confidence: 99%

Essential roles of 11β-HSD1 in regulating brown adipocyte function

Liu

Kong²,

Wang³

et al. 2012

Journal of Molecular Endocrinology

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Brown adipose tissue (BAT) increases energy expenditure and is an attractive therapeutic target for obesity. 11b-Hydroxysteroid dehydrogenase type 1 (11b-HSD1), an amplifier of local glucocorticoid activity, has been shown to modulate white adipose tissue (WAT) metabolism and function. In this study, we investigated the roles of 11b-HSD1 in regulating BAT function. We observed a significant increase in the expression of BAT-specific genes, including UCP1, Cidea, Cox7a1, and Cox8b, in BVT.2733 (a selective inhibitor of 11b-HSD1)-treated and 11b-HSD1-deficient primary brown adipocytes of mice. By contrast, a remarkable decrease in BAT-specific gene expression was detected in brown adipocytes when 11b-HSD1 was overexpressed, which effect was reversed by BVT.2733 treatment. Consistent with the in vitro results, expression of a range of genes related to brown fat function in high-fat diet-fed mice treated with BVT.2733. Our results indicate that 11b-HSD1 acts as a vital regulator that controls the expression of genes related to brown fat function and as such may become a potential target in preventing obesity.

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“…Overexpression of the 11βHSD1 gene in mice is associated with enhanced adipocyte differentiation and higher adipose tissue mass [2]. Increased 11βHSD1 gene expression has also been found in the adipose tissue of obese Zucker rats [3] and in the adipose tissue of morbidly obese patients [4][5][6][7][8]. It has been postulated that increased activation of glucocorticosteroids in adipose tissue (due to increased 11βHSD1 activity) plays an important role in the development of central obesity and metabolic syndrome [1,[9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Chronic food restriction up-regulates 11-β-hydroxysteroid dehydrogenase

et al. 2011

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Corticosterone — product of 11-β-hydroxysteroid dehydrogenase type I (11βHSD1) stimulates adipocytes differentiation and activates lipogenic enzymes gene expression in white adipose tissue (WAT) of rats. The aim of the study was to examine the effect of chronic food restriction, often practised by obese individuals trying to lose body mass, on: a) 11βHSD1 gene expression, b) expression of genes associated with adipocyte differentiation (PPARg, SREBP-1, adiponectin), and c) expression of genes associated with lipogenesis in WAT of rats. Two-month old rats were divided into a control and a food restricted group obtaining 50% of food consumed by controls for 30 days. mRNA levels of studied genes in perirenal WAT were analysed by real-time PCR. 11βHSD1 and lipogenic enzymes activities were measured by radiometric conversion assay and by spectrophotometric assay respectively. Food restriction caused significant increase of 11βHSD1, PPARg, SREBP1, adiponectin and lipogenic enzymes mRNA levels in perirenal WAT. 11βHSD1 and some lipogenic enzymes activities were also increased by food restriction. The coordinated up-regulation of 11βHSD1, and genes associated with adipocyte differentiation and lipogenesis by food restriction suggests that such nutritional condition shifts WAT metabolism, that would permit this tissue to synthesize and accumulate triacylglycerols immediately after refeeding.

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Overexpression of 11β-Hydroxysteroid Dehydrogenase Type 1 in Hepatic and Visceral Adipose Tissue is Associated with Metabolic Disorders in Morbidly Obese Patients

Cited by 58 publications

References 49 publications

Cortisol in tissue and systemic level as a contributing factor to the development of metabolic syndrome in severely obese patients

Cortisol in tissue and systemic level as a contributing factor to the development of metabolic syndrome in severely obese patients

Essential roles of 11β-HSD1 in regulating brown adipocyte function

Chronic food restriction up-regulates 11-β-hydroxysteroid dehydrogenase

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