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.

Association of Body Fat Mass and Fat Distribution With the Incidence of Hypertension in a Population‐Based Chinese Cohort: A 22‐Year Follow‐Up

“…Using the body mass index (BMI), many studies have reported that overweight and obesity are major independent risk factors for hypertension,12, 13, 14, 15, 16, 17, 18 with ≈65% to 78% of adult hypertension cases being attributable to obesity at the population level 19. Indeed, the prevalence of hypertension is reported to be 35% to 50% in overweight and obese adults, which is approximately double the reported prevalence of 23% in individuals of normal weight 20.…”

Novel Methods in Pulmonary Hypertension Phenotyping in the Age of Precision Medicine (2015 Grover Conference Series)

“…Studies have shown that leptin levels are related to cardiovascular function. 54 Independent of obesity, leptin levels have been shown to be inversely proportional to cardiovascular mortality in coronary artery disease and diabetes. 55,56 The cardioprotectiveness of leptin is most likely due to its anti-inflammatory, proapoptotic, and antithrombotic actions.…”

Very low-density lipoprotein (VLDL)-induced signals mediating aldosterone production

“…For example, a recent study demonstrated a role for adipocyte-released leptin, the serum levels of which are proportional to fat mass, in regulating aldosterone levels both in vitro and in vivo (Huby et al 2015 andreviewed in Xie &Bollag 2016). Other studies have suggested effects of adipocyte-released cytokines, or adipokines, such as tumor necrosis factor-α, interleukin-6 and complement-C1q TNF-related protein 1 (CTRP1) (Jeon et al 2008), on aldosterone levels as well (Briet & Schiffrin 2011, Xie & Bollag 2016. Therefore, it is clear that further studies are needed to define not only the complete pathway through which VLDL promotes aldosterone production in the adrenal zona glomerulosa but also the possible involvement of other adipokines and adipocyte-derived factors.…”

“…The results from these studies suggest the importance of aldosterone in cardiac pathologies. In addition, several reports have suggested that aldosterone may be one of the causal links between obesity and hypertension (Briet & Schiffrin 2011, Kawarazaki & Fujita 2016, Xie & Bollag 2016, although the mechanism(s) underlying this association among obesity, aldosterone and high blood pressure are unclear. Nevertheless, because of the profound effects that aldosterone can exert on the cardiovascular system, understanding the regulation of its biosynthesis is important, particularly as aldosterone may exert functions independently of the MR, such that MR antagonists may not completely inhibit all of aldosterone's adverse effects (e.g., Hofmann et al 2016).…”