Expression of genes related to glucocorticoid action in human subcutaneous and omental adipose tissue

Veilleux, Alain; Laberge, Philippe Y.; Morency, Jacques; Noël, Suzanne; Luu‐The, Van; Tchernof, André

doi:10.1016/j.jsbmb.2010.02.024

Cited by 54 publications

(57 citation statements)

References 29 publications

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“…Our results now support the presence of an additional regulatory mechanism of adipogenesis by these hormones. Higher 11␤-HSD1 reductase activity and local cortisol concentrations were observed in omental compared with subcutaneous adipose tissue of viscerally obese subjects (24,25). In this study, we show that DHT inactivation rates were more strongly induced by glucocorticoids in omental compared with subcutaneous adipose tissue of obese subjects.…”

Section: Discussionsupporting

confidence: 48%

“…Primer sequences for AKR1C1 (5=-CCT-ATA-GTG-CTC-TGG-GAT-CCC-AC-3=/5=-AGG-ACC-ACA-ACC-CCA-CGC-TGT), AKR1C2 (5=-CCG-TCA-AAT-TGG-CAA-TAG-AAG-CC-3=/5=-CAA-CTC-TGG-TCG-ATG-GGA-ATT-GCT), and AKR1C3(5=-CAA-CCA-GGT-AGA-ATG-TCA-TCC-GTA-T-3=/5=-ACC-CAT-CGT-TTG-TCT-CGT-TGA) and fatty acid-binding protein 4 (FABP4; 5=-TGG-GCC-AGG-AAT-TTG-ACG-AAG-AC-3=/ 5=-CGT-CCC-TTG-GCT-TAT-GCT-CTC-T) were designed using GeneTools (Biotools). Results were expressed as relative units compared with Atp5o housekeeping gene expression (24).…”

Section: Table 1 Gre In the Promoter Region Of Akr1c Genesmentioning

confidence: 99%

“…Active glucocorticoids such as cortisol are strong modulators of adipose tissue metabolism because they can alter body fat distribution (16,24,25) by impeding cellular proliferation and promoting differentiation of preadipocytes to mature adipocytes (10,12). Stimulatory effects of glucocorticoids on preadipocyte differentiation are believed to involve the induction of lipoprotein lipase and glycerol-3-phosphate dehydrogenase (G3PDH) expression (10,12,17).…”

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confidence: 99%

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Glucocorticoid-induced androgen inactivation by aldo-keto reductase 1C2 promotes adipogenesis in human preadipocytes

Veilleux

Côté

Blouin

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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-The, Tchernof A. Glucocorticoid-induced androgen inactivation by aldo-keto reductase 1C2 promotes adipogenesis in human preadipocytes. Am J Physiol Endocrinol Metab 302: E941-E949, 2012. First published January 24, 2012; doi:10.1152/ajpendo.00069.2011.-Adipogenesis and lipid storage in human adipose tissue are inhibited by androgens such as DHT. Inactivation of DHT to 3␣-diol is stimulated by glucocorticoids in human preadipocytes. We sought to characterize glucocorticoid-induced androgen inactivation in human preadipocytes and to establish its role in the antiadipogenic action of DHT. Subcutaneous and omental primary preadipocyte cultures were established from fat samples obtained in subjects undergoing abdominal surgeries. Inactivation of DHT to 3␣/␤-diol for 24 h was measured in dexamethasone-or vehicle-treated cells. Specific downregulation of aldo-keto reductase 1C (AKR1C) enzymes in human preadipocytes was achieved using RNA interference. In whole adipose tissue sample, cortisol production was positively correlated with androgen inactivation in both subcutaneous and omental adipose tissue (P Ͻ 0.05). Maximal dexamethasone (1 M) stimulation of DHT inactivation was higher in omental compared with subcutaneous fat from men as well as subcutaneous and omental fat from women (P Ͻ 0.05). A significant positive correlation was observed between BMI and maximal dexamethasone-induced DHT inactivation rates in subcutaneous and omental adipose tissue of men and women (r ϭ 0.24, n ϭ 26, P Ͻ 0.01). siRNA-induced downregulation of AKR1C2, but not AKR1C1 or AKR1C3, significantly reduced basal and glucocorticoid-induced androgen inactivation rates (P Ͻ 0.05). The inhibitory action of DHT on preadipocyte differentiation was potentiated following AKR1C2 but not AKR1C1 or AKR1C3 downregulation. Specifically, lipid accumulation, G3PDH activity, and FABP4 mRNA expression in differentiated preadipocytes exposed to DHT were reduced further upon AKR1C2 siRNA transfection. We conclude that glucocorticoid-induced androgen inactivation is mediated by AKR1C2 and is particularly effective in omental preadipocytes of obese men. The interplay between glucocorticoids and AKR1C2-dependent androgen inactivation may locally modulate adipogenesis and lipid accumulation in a depot-specific manner.3␣-hydroxysteroid dehydrogenase; 5␣-dihydrotestosterone; dexamethasone THE PROPENSITY TO ACCUMULATE LIPIDS in the visceral rather than in the subcutaneous adipose tissue compartment is associated with metabolic disorders. Little is known about the factors leading to preferential visceral fat accumulation when facing excess energy intake, but steroid hormones such as glucocorticoids and androgens appear to play a key role.

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Section: Discussionsupporting

confidence: 48%

Section: Table 1 Gre In the Promoter Region Of Akr1c Genesmentioning

confidence: 99%

mentioning

confidence: 99%

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Glucocorticoid-induced androgen inactivation by aldo-keto reductase 1C2 promotes adipogenesis in human preadipocytes

Veilleux

Côté

Blouin

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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“…VAT is thought to be differentially responsive to GCs than subcutaneous fat (SAT). Indeed, GC binding to tissue homogenates and GR mRNA expression is higher in omental fat than in SAT (67,68). Moreover, GCs were able to induce insulin resistance in human omental but not in subcutaneous adipocytes (69).…”

Section: Gcs and Obesitymentioning

confidence: 97%

Metabolic comorbidities in Cushing's syndrome

Ferraú

Korbonits

2015

European Journal of Endocrinology

149

121

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Cushing's syndrome (CS) patients have increased mortality primarily due to cardiovascular events induced by glucocorticoid (GC) excess-related severe metabolic changes. Glucose metabolism abnormalities are common in CS due to increased gluconeogenesis, disruption of insulin signalling with reduced glucose uptake and disposal of glucose and altered insulin secretion, consequent to the combination of GCs effects on liver, muscle, adipose tissue and pancreas. Dyslipidaemia is a frequent feature in CS as a result of GC-induced increased lipolysis, lipid mobilisation, liponeogenesis and adipogenesis. Protein metabolism is severely affected by GC excess via complex direct and indirect stimulation of protein breakdown and inhibition of protein synthesis, which can lead to muscle loss. CS patients show changes in body composition, with fat redistribution resulting in accumulation of central adipose tissue. Metabolic changes, altered adipokine release, GC-induced heart and vasculature abnormalities, hypertension and atherosclerosis contribute to the increased cardiovascular morbidity and mortality. In paediatric CS patients, the interplay between GC and the GH/IGF1 axis affects growth and body composition, while in adults it further contributes to the metabolic derangement. GC excess has a myriad of deleterious effects and here we attempt to summarise the metabolic comorbidities related to CS and their management in the perspective of reducing the cardiovascular risk and mortality overall.

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“…One study reported low rates of glucocorticoid uptake and release by adipose tissue, suggesting that adipose tissues are isolated from rapid circadian changes in circulating glucocorticoids (227). Expression levels and in vitro activity of 11␤-HSD-1 are generally higher in visceral compared with subcutaneous adipose tissue (74,371,587,588), although this is not unanimous (104,417,568 (371,587,588). We have shown that relatively elevated 11␤-HSD1 oxoreductase activity in visceral compared with subcutaneous adipose tissue is associated with increased visceral fat accumulation as well as with concomitant metabolic alterations, independent of overall obesity levels (587, 588).…”

Section: H Hypothalamo-pituitary-adrenal Axis Stress and Glucocortmentioning

confidence: 99%

Pathophysiology of Human Visceral Obesity: An Update

Tchernof

Després

2013

Physiological Reviews

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LTchernof A, Després J-P. Pathophysiology of Human Visceral Obesity: An Update. Physiol Rev 93: 359 -404, 2013; doi:10.1152/physrev.00033.2011.-Excess intra-abdominal adipose tissue accumulation, often termed visceral obesity, is part of a phenotype including dysfunctional subcutaneous adipose tissue expansion and ectopic triglyceride storage closely related to clustering cardiometabolic risk factors. Hypertriglyceridemia; increased free fatty acid availability; adipose tissue release of proinflammatory cytokines; liver insulin resistance and inflammation; increased liver VLDL synthesis and secretion; reduced clearance of triglyceride-rich lipoproteins; presence of small, dense LDL particles; and reduced HDL cholesterol levels are among the many metabolic alterations closely related to this condition. Age, gender, genetics, and ethnicity are broad etiological factors contributing to variation in visceral adipose tissue accumulation. Specific mechanisms responsible for proportionally increased visceral fat storage when facing positive energy balance and weight gain may involve sex hormones, local cortisol production in abdominal adipose tissues, endocannabinoids, growth hormone, and dietary fructose. Physiological characteristics of abdominal adipose tissues such as adipocyte size and number, lipolytic responsiveness, lipid storage capacity, and inflammatory cytokine production are significant correlates and even possible determinants of the increased cardiometabolic risk associated with visceral obesity. Thiazolidinediones, estrogen replacement in postmenopausal women, and testosterone replacement in androgen-deficient men have been shown to favorably modulate body fat distribution and cardiometabolic risk to various degrees. However, some of these therapies must now be considered in the context of their serious side effects. Lifestyle interventions leading to weight loss generally induce preferential mobilization of visceral fat. In clinical practice, measuring waist circumference in addition to the body mass index could be helpful for the identification and management of a subgroup of overweight or obese patients at high cardiometabolic risk.

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Expression of genes related to glucocorticoid action in human subcutaneous and omental adipose tissue

Cited by 54 publications

References 29 publications

Glucocorticoid-induced androgen inactivation by aldo-keto reductase 1C2 promotes adipogenesis in human preadipocytes

Glucocorticoid-induced androgen inactivation by aldo-keto reductase 1C2 promotes adipogenesis in human preadipocytes

Metabolic comorbidities in Cushing's syndrome

Pathophysiology of Human Visceral Obesity: An Update

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