Abstract
ObjectiveObesity is associated with an increased risk of diabetes mellitus, hypertension, and renal dysfunction. Angiotensin 1–7 and alamandine are heptameric renin angiotensin system peptide hormones. Further, alamandine levels increase with renal dysfunction. In the cardiovascular system, angiotensin 1–7 and alamandine produce similar improvements and counterbalance angiotensin II in regulating vascular function. We aimed to determine whether the effect of alamandine on leptin expression and secretion in adipocytes was similar to that of angiotensin 1–7.Approach and resultsWe studied isolated peri-renal visceral adipose tissue and peri-renal isolated visceral adipocytes from male Wistar rats. Angiotensin II from 0.01 to 10nM had no effect on leptin expression. Angiotensin 1–7 (1 nM) increased leptin secretion and expression, whereas alamandine (1 nM) decreased leptin secretion and expression in adipose tissue and isolated adipocytes and reduced blood leptin levels in vivo. These effects were mediated by Gq, c-Src, p38 mitogen-activated protein, and IκB activation. Additionally, alamandine induced nitric oxide expression via inducible nitric oxidase synthase and plasminogen activator inhibitor 1 expression in adipose tissue and isolated adipocytes.ConclusionsAngiotensin 1–7 and alamandine produced opposing effects on leptin expression and secretion in adipose tissue. This result suggests that the action of Mas (angiotensin 1–7 receptor) and Mas-related G-protein coupled receptor D in adipocytes exhibited opposing actions similar to angiotensin II type 1 and type 2 receptors.
Highlights
The renin angiotensin system (RAS) regulates circulating blood volume and blood pressure, and is involved in vascular endothelial function and cardiac muscle hyperplasia [1,2,3]
Angiotensin 1–7 and alamandine produced opposing effects on leptin expression and secretion in adipose tissue. This result suggests that the action of Mas and Mas-related G-protein coupled receptor D in adipocytes exhibited opposing actions similar to angiotensin II type 1 and type 2 receptors
The angiotensin 1–7 (Ang1-7) receptor was identified as the Mas receptor in 2003 [6, 7], and the alamandine receptor was identified as the Mas-related G protein-coupled receptor D (MrgD) in 2013 [5, 8]
Summary
The renin angiotensin system (RAS) regulates circulating blood volume and blood pressure, and is involved in vascular endothelial function and cardiac muscle hyperplasia [1,2,3]. Angiotensin II (AngII) is an octameric peptide hormone that is a RAS component. There are two kinds of AngII receptor, which have opposing actions [3]. Angiotensin 1–7 (Ang1-7) and alamandine are heptameric RAS peptide hormones [4, 5] (S1A Fig) that differ in a single C-terminal amino acid. The Ang receptor was identified as the Mas receptor in 2003 [6, 7], and the alamandine receptor was identified as the Mas-related G protein-coupled receptor D (MrgD) in 2013 [5, 8]. MrgD receptors are mainly expressed in dorsal root and sensory ganglia; moderately expressed in testes, urinary bladder, artery, and uterus; and slightly expressed in cerebellum, brown adipose, white adipose, and gastrointestinal tract [9] [10] [11]. Mas (Ang receptor) is more broadly expressed than most other Mrg receptors
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