Dehydroepiandrosterone (DHEA) treatment in vitro inhibits adipogenesis in human omental but not subcutaneous adipose tissue

Rice, Samuel Peter Llewellyn; Zhang, Lei; Grennan-Jones, Fiona; Agarwal, Neera; Lewis, Mark; Rees, Dafydd Aled; Ludgate, Marian

doi:10.1016/j.mce.2010.02.017

Cited by 43 publications

(36 citation statements)

References 39 publications

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“…However, the effects of estrogens on adipocyte differentiation, rather than proliferation, are more varied (Dieudonne et al 2000, Anderson et al 2001, Gupta et al 2008, Rice et al 2010. Pre-adipocytes express only ESR1, therefore, all estrogenic effects on adipogenesis are presumably mediated through the action of this receptor (Pallottini et al 2008).…”

Section: Adipocyte Differentiationmentioning

confidence: 99%

“…This choice of androgen treatment is likely due to the fact that circulating DHEA has a negative correlation with abdominal WAT accumulation in men (Couillard et al 2000). A recent study using primary human pre-adipocytes found that DHEA had no effect on subcutaneous pre-adipocyte differentiation but decreased adipogenesis in omental pre-adipocytes (Rice et al 2010). The 3T3-L1 pre-adipocyte cell line has been used extensively to assess the effects of androgens on adipogenesis and has shown varying responses.…”

Section: R142mentioning

confidence: 99%

“…The 3T3-L1 pre-adipocyte cell line has been used extensively to assess the effects of androgens on adipogenesis and has shown varying responses. Some studies have found that DHEA reduces both the proliferation and differentiation of 3T3-L1 cells (LeaCurrie et al 1998), whereas other studies have shown no effect of DHEA on 3T3-L1 adipogenesis (Rice et al 2010). However, 3T3-L1 cells are losing favor for the study of pre-adipocyte and adipocyte cell behavior, as they may not recapitulate the physiology of primary cells.…”

Section: R142mentioning

confidence: 99%

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The role of sex steroids in white adipose tissue adipocyte function

Newell-Fugate

2017

Reproduction

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Abstractwith the increasing knowledge that gender influences normal physiology, much biomedical research has begun to focus on the differential effects of sex on tissue function. Sexual dimorphism in mammals is due to the combined effects of both genetic and hormonal factors. Hormonal factors are mutable particularly in females in whom the estrous cycle dominates the hormonal milieu. Given the severity of the obesity epidemic and the fact that there are differences in the obesity rates in men and women, the role of sex in white adipose tissue function is being recognized as increasingly important. Although sex differences in white adipose tissue distribution are well established, the mechanisms affecting differential function of adipocytes within white adipose tissue in males and females remain largely understudied and poorly understood. One of the largest differences in the endocrine environment in males and females is the concentration of circulating androgens and estrogens. This review examines the effects of androgens and estrogens on lipolysis/lipogenesis, adipocyte differentiation, insulin sensitivity and adipokine production in adipocytes from white adipose tissue with a specific emphasis on the sexual dimorphism of adipocyte function in white adipose tissue during both health and disease.Reproduction (2017) 153 R133-R149

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Section: Adipocyte Differentiationmentioning

confidence: 99%

Section: R142mentioning

confidence: 99%

Section: R142mentioning

confidence: 99%

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The role of sex steroids in white adipose tissue adipocyte function

Newell-Fugate

2017

Reproduction

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“…These cells transform into preadipocytes, which are difficult to distinguish from stem cells, proliferate, and then terminally differentiate into mature adipocytes (40). Because proliferative activity is considered to be eliminated in mature adipocytes (16), we noted a nonmature adipocyte fraction of adipose tissue, stromal vascular fraction (SVF), consisting of adipocyte progenitor cells, mature endothelial cells, and angiogenic progenitor cells (38), and immune cells including macrophages (47). Newborn adipocytes are provided from the SVF, and the efficacy of adipogenesis vastly influences adiposity and insulin sensitivity (54).…”

mentioning

confidence: 99%

Dehydroepiandrosterone reduces preadipocyte proliferation via androgen receptor

Fujioka¹,

Kajita²,

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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Several studies have suggested that both testosterone and dehydroepiandrosterone (DHEA) have weight-reducing and antidiabetic effects, especially in rodent studies; however, the precise mechanism of their action remains unclear. Here, we investigated the effect of DHEA on cell growth in adipose tissue. The appearance of senescence-associated β-galactosidase in stromal vascular fraction (SVF) isolated from Otsuka Long-Evans Tokushima fatty rats, an animal model of inherent obese type 2 diabetes, was prevented by DHEA administration. Next, the effects of DHEA and testosterone were compared in vivo and in vitro to evaluate whether these hormones influence cell growth in adipose tissue. Both DHEA and testosterone reduced body weight and epididymal fat weight equivalently when administered for 4 wk. To assess the effect of DHEA and testosterone on cell growth in adipose tissue, 5-bromo-2'-deoxyuridine (BrdU) uptake by SVF was measured. Quantification analysis of BrdU uptake by examining DNA isolated from each SVF revealed that treatment with DHEA and testosterone reduced cell replication. These results indicated that DHEA- and testosterone-induced decreased adiposity was associated with reduced SVF growth. Incubation with DHEA and testosterone equally decreased BrdU uptake by 3T3-L1 preadipocytes. Pretreatment with the androgen receptor (AR) inhibitor flutamide, but not the estrogen receptor inhibitor fulvestrant, abolished these effects. Knockdown of AR with siRNA also inhibited DHEA-induced decreases in BrdU uptake. These results suggest that DHEA-induced growth suppression of preadipocytes is mediated via AR. Therefore, both DHEA and testosterone similarly decrease adipocyte growth possibly via a common mechanism.

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“…In vitro studies have shown that DHEA inhibits the proliferation and differentiation of adipocytes [16,32,33]. In cultured human omental and subcutaneous preadipocytes, DHEA added at physiological concentrations suppressed cell proliferation [32].…”

Section: Dhea Reduces Adipose Tissue Mass and Inhibits Adipogenesismentioning

confidence: 99%

Effects of DHEA on metabolic and endocrine functions of adipose tissue

Karbowska

Kochan

2013

Hormone Molecular Biology and Clinical Investigation

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Dehydroepiandrosterone (DHEA) and its sulfate ester, DHEAS, are the major circulating adrenal steroids and serve as substrates for sex hormone biosynthesis. DHEA is effectively taken up by adipose tissue, where the concentrations of free DHEA are four to ten times higher than those found in the circulation. DHEA reduces adipose tissue mass and inhibits the proliferation and differentiation of adipocytes; it may also protect against obesity by lowering the activity of stearoyl-CoA desaturase 1 in fat cells. Recent studies demonstrate that DHEA stimulates triacylglycerol hydrolysis in adipose tissue by increasing the expression and activity of adipose triglyceride lipase and hormone-sensitive lipase, the key enzymes of lipolysis. DHEA has been shown to modulate insulin signaling pathways, enhance glucose uptake in adipocytes, and increase insulin sensitivity in patients with DHEA deficiency or abnormal glucose tolerance. Additionally, by suppressing the activity of 11β-hydroxysteroid dehydrogenase 1 in adipocytes, DHEA may promote intra-adipose inactivation of cortisol to cortisone. Several studies have demonstrated that DHEA may also regulate the expression and secretion of adipokines such as leptin, adiponectin, and resistin. The effects of DHEA on adipokine expression in adipose tissue are depot-specific, with visceral fat being the most responsive. The mechanisms underlying DHEA actions in adipose tissue are still unclear; however, they involve nuclear receptors such as androgen receptor and peroxisome proliferator-activated receptors γ and α. Because clinical trials investigating the effects of DHEA failed to yield consistent results, further studies are needed to clarify the role of DHEA in the regulation of human adipose tissue physiology.

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Dehydroepiandrosterone (DHEA) treatment in vitro inhibits adipogenesis in human omental but not subcutaneous adipose tissue

Cited by 43 publications

References 39 publications

The role of sex steroids in white adipose tissue adipocyte function

The role of sex steroids in white adipose tissue adipocyte function

Dehydroepiandrosterone reduces preadipocyte proliferation via androgen receptor

Effects of DHEA on metabolic and endocrine functions of adipose tissue

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