Obesity, hypertension and aldosterone: is leptin the link?

Abstract

Obesity is a serious health hazard with rapidly increasing prevalence in the United States. In 2014, the World Health Organization estimated that nearly 2 billion people worldwide were overweight with an estimated 600 million of these obese. Obesity is associated with many chronic diseases, including cardiovascular disease and hypertension. Data from the Framingham Heart study suggest that approximately 78% of the risk for hypertension in men and 65% in women is related to excess body weight, a relationship that is further supported by studies showing increases in blood pressure with weight gain and decreases with weight loss. However, the exact mechanism by which excess body fat induces hypertension remains poorly understood. Several clinical studies have demonstrated elevated plasma aldosterone levels in obese individuals, especially those with visceral adiposity, with decreased aldosterone levels measured in concert with reduced blood pressure following weight loss. Since aldosterone is a mineralocorticoid hormone that regulates blood volume and pressure, serum aldosterone levels may link obesity and hypertension. Nevertheless, the mechanism by which obesity induces aldosterone production is unclear. A recent study by Belin de Chantemele and coworkers suggests that one adipose-released factor, leptin, is a direct agonist for aldosterone secretion; other adipose-related factors may also contribute to elevated aldosterone levels in obesity, such as very low-density lipoprotein (VLDL), the levels of which are elevated in obesity and which also directly stimulates aldosterone biosynthesis. This focused review explores the possible roles of leptin and VLDL in modulating aldosterone secretion to underlie obesity-associated hypertension.

Keywords: adipose tissue; aldosterone; hypertension; leptin; obesity.

Figure 1.

Obesity increases blood pressure. Excess fat deposits (including those surrounding the adrenal glands) of obese individuals secrete large amounts of leptin. The data of Belin de Chantemele and coworkers indicate that this adipose-derived leptin can stimulate zona glomerulosa cells of the adrenal gland to produce aldosterone. Aldosterone, in turn, causes the kidney to retain salt and water, raising blood volume and pressure. Aldosterone can also produce endothelial dysfunction and cardiac fibrosis. Obesity also results in dyslipidemia, including increased serum levels of VLDL; this lipoprotein has also been shown to induce aldosterone production. Other mechanisms (not illustrated) that potentially underlie obesity-associated hypertension include increased levels of proinflammatory cytokines, hypersecretion of various adipokines and/or excessive activity of the sympathetic nervous or renin-angiotensin II-aldosterone systems.