Aldosterone and the Mineralocorticoid Receptor: Risk Factors for Cardiometabolic Disorders

Garg, Rajesh; Adler, Gail K.

doi:10.1007/s11906-015-0567-8

Cited by 22 publications

(15 citation statements)

References 85 publications

(50 reference statements)

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“…It has also been reported that patients with primary aldosteronism have an increased incidence of IR that it is mediated by a diminished expression of genes involved in lipid metabolism in visceral adipose tissue compared to that of sex, age, and BMI-matched controls (49). Moreover, aldosterone has different effects on insulin metabolism, among others, interferes with insulin signaling pathways, reduces insulin receptor gene transcription and enhances degradation of insulin receptor substrates and is able to increase oxidative stress and inflammation (50).…”

Section: Discussionmentioning

confidence: 98%

Eplerenone Implantation Improved Adipose Dysfunction Averting RAAS Activation and Cell Division

et al. 2020

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Introduction: Mineralocorticoid receptor (MR) activation within adipose tissue, triggers inflammation and metabolic syndrome development. The pharmacological blockade of MR provides beneficial effects for adipose tissue. Our study evaluates the impact of eplerenone implantation upon obesity. Experimental approach: A group of mice with implanted placebo pellets were fed using two types of diet, a normal (ND) or a high fat (HFD) diet. Additionally, a group of mice fed HFD were implanted with an eplerenone pellet. Metabolic and biochemical parameters were assessed in each animal group. Adipocyte size and lipid accumulation were investigated in the liver and adipose tissue. We evaluated the components of renin-angiotensin-aldosterone system (RAAS) locally in adipose tissue. Key results: Eplerenone reduced HFD-induced body weight gain, fasting glucose levels, fat accumulation, HFD-induced adipocyte size and liver lipid accumulation and improved glucose tolerance. In the adipose tissue, HFD significantly increased the mRNA levels of the RAAS molecules relative to the ND group. Eplerenone lowered RAAS mRNA levels, components of lipid metabolism and markers of inflammation in HFD-fed animals. Conclusion: MR antagonism with eplerenone diminishes insulin resistance that is related to obesity partly via a reduction of RAAS activation, inflammatory progression and cytokines induction. This suggests that eplerenone should be further studied as a therapeutic option for obesity and overweight.

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Section: Discussionmentioning

confidence: 98%

Eplerenone Implantation Improved Adipose Dysfunction Averting RAAS Activation and Cell Division

et al. 2020

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“…Steroid hormones play important roles in the regulation of many physiological processes, including mineralocorticoid and glucose homeostasis or sexual differentiation [1][2][3]. Several steroids are linked to diseases such as obesity, obesity-induced hypertension and type 2 diabetes [4][5][6]. Adrenal glands and reproductive organs are the major sites of steroid hormone biosynthesis; cholesterol is the common precursor [2,7].…”

Section: Introductionmentioning

confidence: 99%

Elevated Steroid Hormone Production in the db/db Mouse Model of Obesity and Type 2 Diabetes

et al. 2016

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Obesity and type 2 diabetes have become a major public health problem worldwide. Steroid hormone dysfunction appears to be linked to development of obesity and type 2 diabetes and correction of steroid abnormalities may offer new approaches to therapy. We therefore analyzed plasma steroids in 15-16 week old obese and diabetic mice using liquid chromatography-tandem mass spectrometry. Lean served as controls. mice developed obesity, hyperglycemia, hyperleptinemia, and hyperlipidemia. Hepatic triglyceride storage was increased and adiponectin and pancreatic insulin were lowered. Aldosterone, corticosterone, 11-deoxycorticosterone, and progesterone were respectively increased by 3.6-, 2.9-, 3.4, and 1.7-fold in mice compared to controls. Ratios of aldosterone-to-progesterone and corticosterone-to-progesterone were respectively 2.0- and 1.5-fold higher in mice. Genes associated with steroidogenesis were quantified in the adrenal glands and gonadal adipose tissues. In adrenals,, ,, ,, and were all significantly increased in mice compared with controls. In adipose tissue, no or transcripts were detected and no differences in, ,, or expression were found between and mice. In conclusion, the present study showed an elevated steroid hormone production and adrenal steroidogenesis in the model of obesity and type 2 diabetes.

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“…Other extrarenal tissue that express MR is the adipose tissue where MR is involved in essential processes such as differentiation, autophagy, and adipokine secretion [4,77]. MR expression is increased in adipose tissue of murine models of obesity and in obese human subjects, and different studies using MR antagonists and also adipocyte-specific MR transgenic mice have demonstrated a key role of MR in insulin signaling and inflammation, as reviewed previously [4, 77,78].…”

Section: Mr and Oxidative Stress In Adipose Tissuementioning

confidence: 99%

Aldosterone/MR Signaling, Oxidative Stress, and Vascular Dysfunction

Briones¹,

Touyz²

2019

Aldosterone-Mineralocorticoid Receptor - Cell Biology to Translational Medicine

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The mineralocorticoid receptor (MR) is a transcription factor of the family of steroid receptors that classically binds the hormone aldosterone. The contribution of MR in the regulation of sodium retention and blood pressure is well known. However, MR is expressed in extrarenal tissues including endothelial and vascular smooth muscle cells, and its activation leads to vascular remodeling, vascular stiffness, and endothelial dysfunction leading to vascular damage, an important pathophysiological process in hypertension and other cardiovascular diseases. Moreover, MR is expressed in nonvascular cells in close contact with the vascular wall including immune cells and adipocytes that might influence vascular function and structure. MR activation involves its translocation to the nucleus and regulation of gene transcription. In addition, aldosterone exerts rapid non-genomic effects mediated by MR-dependent and MR-independent mechanisms. Both genomic and non-genomic effects facilitate reactive oxygen species (ROS) production (particularly by the enzyme NADPH oxidase), inflammation, and fibrosis, which, in turn, promote tissue remodeling, vascular stiffening, and endothelial dysfunction. Studies with MR antagonists and experimental models with cell-specific knockout or overexpression of MR further support a role for aldosterone/MR-mediated oxidative stress-dependent processes in vascular damage. This review focuses on the relationship between aldosterone/MR signaling and oxidative stress and the implications in vascular regulation in health and disease.

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Aldosterone and the Mineralocorticoid Receptor: Risk Factors for Cardiometabolic Disorders

Cited by 22 publications

References 85 publications

Eplerenone Implantation Improved Adipose Dysfunction Averting RAAS Activation and Cell Division

Eplerenone Implantation Improved Adipose Dysfunction Averting RAAS Activation and Cell Division

Elevated Steroid Hormone Production in the db/db Mouse Model of Obesity and Type 2 Diabetes

Aldosterone/MR Signaling, Oxidative Stress, and Vascular Dysfunction

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