Antiadipogenic Effects of the Mineralocorticoid Receptor Antagonist Drospirenone: Potential Implications for the Treatment of Metabolic Syndrome

Caprio, Massimiliano; Antelmi, Antonella; Chétrite, G.; Muscat, Adeline; Mammi, Caterina; Marzolla, Vincenzo; Fabbri, Andrea; Zennaro, Maria-Christina; Fève, Bruno

doi:10.1210/en.2010-0674

Cited by 123 publications

(88 citation statements)

References 41 publications

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“…Thereby, DRSP may display favorable metabolic effects in women, in adequate combination with estrogens, to prevent excessive adipose tissue deposition and its related cardiometabolic complications (75).…”

Section: Medical Intervention In Pcosmentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Recent advances in cardiovascular aspects of polycystic ovary syndrome

Sathyapalan

Atkin²

2012

European Journal of Endocrinology

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Polycystic ovary syndrome (PCOS) has been associated with increased cardiovascular risk (CVR) markers, but population studies have not clarified whether there is an increase in cardiovascular morbidity and mortality. Four different PCOS phenotypes resulted from the Rotterdam criteria that may differ in their CVR potential, thus introducing further complexity. This has led to studies using surrogate CVR markers including biomarkers in blood and imaging such as flow-mediated vasodilatation. In PCOS, both peripheral and central insulin resistance (IR) have been shown. Weight loss has been shown to improve IR and visceral fat, while insulin sensitizer therapies with metformin or thiazolidinediones improve IR and endothelial dysfunction. IR is also found in non-alcoholic fatty liver disease that in turn is very common in PCOS; studies have suggested that IR may be improved by treatment with metformin and omega-3 fish oils. PCOS patients have a more dyslipidemic phenotype that is worse in 'classical PCOS' associated with a higher CVR. Studies with atorvastatin and simvastatin have reported a decrease in the lipid parameters and an improvement in CVR indices including IR, but it is unclear whether this is due to their lipid-lowering action or a pleiotropic effect of the statin. In this expert opinion review, the relevant literature published during the last 2 years was considered. It focuses on some recent important data that has emerged while also exposing the gaps that remain in our knowledge that need to be addressed.

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Section: Medical Intervention In Pcosmentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Recent advances in cardiovascular aspects of polycystic ovary syndrome

Sathyapalan

Atkin²

2012

European Journal of Endocrinology

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“…Other studies evidenced that GR has a more prevalent role, compared with MR, in promoting the maturation of preadipocytes (Lee & Fried 2014a). However, divergent reports showed that MR inhibition blocked the adipogenesis in vitro, whereas downregulation of GR did not (Caprio et al 2007(Caprio et al , 2011. Besides their effects on adipocytes growth, glucocorticoids play a well-known anti-inflammatory role, limiting the obesity-induced inflammation in adipose tissue (Fried et al 1998, Patsouris et al 2009).…”

Section: Introductionmentioning

confidence: 99%

Adipocyte glucocorticoid receptor has a minor contribution in adipose tissue growth

Desarzens

Faresse

2016

Journal of Endocrinology

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The glucocorticoids bind and activate both the glucocorticoid receptor (GR) as well as the mineralocorticoid receptor in adipocytes. Despite several studies to determine the function of these two receptors in mediating glucocorticoids effects, their relative contribution in adipose tissue expansion and obesity is unclear. To investigate the effect of GR in adipose tissue function, we generated an adipocyte-specific Gr-knockout mouse model (Gr ad-ko ). These mice were submitted either to a standard diet or a high-fat high sucrose diet. We found that adipocyte-specific deletion of Gr did not affect body weight gain or adipose tissue formation and distribution. However, the lack of Gr in adipocyte promotes a diet-induced inflammation determined by higher pro-inflammatory genes expression and macrophage infiltration in the fat pads. Surprisingly, the adipose tissue inflammation in Gr ad-ko mice was not correlated with insulin resistance or dyslipidemia, but with disturbed glucose tolerance. Our data demonstrate that adipocyte-specific ablation of Gr in vivo may affect the adipose tissue function but not its expansion during a high calorie diet.

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“…Either knockdown or pharmacological blockade of MR inhibits adipogenesis in 3T3L1 cultures (Caprio et al 2007(Caprio et al , 2011, revealing an important role for this transcription factor in adipose tissue physiology and pathophysiology. Pharmacological MR antagonism has been shown to counteract dysfunctional metabolism of adipose tissue (Guo et al 2008, Hirata et al 2009, Wada et al 2010.…”

Section: Introductionmentioning

confidence: 99%

Cellular mechanisms of MR regulation of adipose tissue physiology and pathophysiology

Armani¹,

Marzolla²,

Fabbri³

et al. 2015

Journal of Molecular Endocrinology

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In addition to the well-documented expression and activity of the mineralocorticoid receptor (MR) in the kidney, in the last decade research on MR has also revealed its important role in regulating functions of extrarenal tissues, including adipose tissue, where MR is involved in adipocyte fundamental processes such as differentiation, autophagy and adipokine secretion. MR expression is increased in adipose tissue of murine models of obesity and in obese human subjects, suggesting that over-activation of the mineralocorticoid signaling leads to dysfunctional adipocyte and associated metabolic disorders. Notably, pharmacological blockade of MR prevents metabolic dysfunctions observed in obese mice and suggests a potential therapeutic use of MR antagonists in the treatment of obesity and metabolic syndrome. However, the molecular pathways affected by MR blockade have been poorly investigated. This review summarizes the functions of MR in the adipocyte, discusses potential signaling pathways mediating MR action, and describes post-translational modifications regulating its activity.

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Antiadipogenic Effects of the Mineralocorticoid Receptor Antagonist Drospirenone: Potential Implications for the Treatment of Metabolic Syndrome

Cited by 123 publications

References 41 publications

MECHANISMS IN ENDOCRINOLOGY: Recent advances in cardiovascular aspects of polycystic ovary syndrome

MECHANISMS IN ENDOCRINOLOGY: Recent advances in cardiovascular aspects of polycystic ovary syndrome

Adipocyte glucocorticoid receptor has a minor contribution in adipose tissue growth

Cellular mechanisms of MR regulation of adipose tissue physiology and pathophysiology

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