Review
Special issue: Endocrine Hypertension
Adipose cell–adrenal interactions: current knowledge and future perspectives

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The central role of adipose tissue in the development of cardiovascular and metabolic pathology has been highlighted by the discovery of mediators (adipokines) secreted by adipose tissue and their involvement in the regulation of various biological processes. In light of recent experimental data, cross-talk between adipose tissue and the adrenal gland, particularly via the mineralocorticoid aldosterone, has been proposed. Aldosterone can induce adipogenesis, and human white adipose tissue is reported to release as-yet-uncharacterized factors that stimulate adrenocortical steroidogenesis and aldosterone production. These data could provide new insights into the pathophysiology of obesity-related disorders, including hypertension and aldosterone excess, with further studies necessary for confirming and better defining such adipose–adrenal interactions.

Introduction

Far from being considered simply a depot for fuel storage, adipose tissue is now recognized as a highly active endocrine organ that can produce and secrete many hormones and proteins, the so-called adipokines, which exert a wide range of biological actions 1, 2. Adipokines are involved in the physiological regulation of adipocyte development and fat storage, glucose homeostasis, lipid metabolism, eating behavior, inflammation and vascular tone; thus, they have a role in obesity-associated disorders, including type 2 diabetes and hypertension.

A link between adipose tissue and the adrenal gland – in particular, glucocorticoids – has already been demonstrated. Both neuroendocrine dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis and alteration of cortisol metabolism might have a role in the pathophysiology of abdominal obesity, development of the metabolic syndrome and cardiovascular disease [3]. Less is known about the interaction between adipose tissue and aldosterone. In this article, we discuss the reciprocal effects of aldosterone on adipose tissue and on adipokine-mediated effects on aldosterone production.

Section snippets

Adipose tissue and the renin–angiotensin–aldosterone system: roles in adipogenesis

Increased levels of circulating angiotensinogen (AGT), renin and aldosterone, and angiotensin-converting enzyme (ACE) activity have been reported in obese patients 4, 5, 6. Increased gene expression in the renin–angiotensin–aldosterone system (RAAS) has been observed in adipose tissue from animal models of obesity and obese human subjects 7, 8, 9. In addition, the role of the local renin–angiotensin system (RAS) in adipocytes has been extensively investigated. Transgenic mice overexpressing

Adipose tissue and the local RAS: role in insulin sensitivity

Angiotensin II (Ang II) and insulin share common intracellular signaling pathways. Stimulation of the Ang II type 1 receptor (AT1R) by Ang II exerts a direct inhibitory effect on insulin-mediated glucose uptake by membrane translocation of the main glucose transporter (GLUT4) [16]. The Ang II type 2 receptor (AT2R) also has a crucial role: whereas angiotensin receptor blocker (ARB) increases insulin-induced glucose uptake in both white and brown adipose tissue, uptake is impaired in the white

Adipose tissue and the adrenal gland: role of aldosterone

The association between high serum aldosterone levels and increased fat mass has been reported in several studies in recent years 23, 24, 25, 26, 27. The association is more evident in women than in men, and weight loss is accompanied by a fall in serum aldosterone levels 27, 28, 29. The mechanisms involved are unclear, although the concomitant reduction of renin levels could contribute per se. Another possible mechanism involves the decrease in levels of aldosterone-stimulating factors

Adipose tissue and the adrenal gland: role of mineralocorticoid-releasing factors

The molecular mechanisms underlying the relationship between obesity and hyperaldosteronism have not been established. Hypotheses that have been proposed include genetic predisposition [36], the involvement of adipose tissue RAS [37] and overactivity of the renal sympathetic nervous system, perhaps leptin induced and responsible for renin release 38, 39. Other proposed molecular mechanisms involve the stimulation of aldosterone secretion by an oxidized derivative of linoleic acid [40] or by

Future perspectives

Adipose-specific mineralocorticoid-stimulating factors need to be identified and characterized. Although the identity of such compounds is unknown, various groups have shown that fat-derived substances induce steroidogenesis in adrenocortical cells and cell lines. Experimental studies of adipose tissue from patients with PA would be extremely helpful for establishing the role of aldosterone excess in adipose tissue homeostasis and adipokine production. After the physiopathological mechanisms of

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