Alamandine reduces leptin expression through the c-Src/p38 MAP kinase pathway in adipose tissue.
Alamandine reduces leptin expression through the c-Src/p38 MAP kinase pathway in adipose tissue.
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DOI：
10.1371/journal.pone.0178769
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Sato K
中科院分区：
文献类型：
--
作者：
Uchiyama T;Okajima F;Mogi C;Tobo A;Tomono S;Sato K
肥胖与糖尿病、高血压和肾功能不全的风险增加有关。血管紧张素1-7和alamandine是七聚体肾素血管紧张素系统肽激素。此外，alamandine水平随着肾功能障碍而增加。在心血管系统中，血管紧张素1-7和alamandine产生类似的改善作用，并在调节血管功能方面抵消血管紧张素II。我们的目的是确定阿拉曼定对脂肪细胞中瘦素表达和分泌的影响是否与血管紧张素1-7相似。我们研究了雄性Wistar大鼠离体肾周内脏脂肪组织和离体肾周内脏脂肪细胞。0.01 - 10 nM的血管紧张素II对瘦素表达没有影响。血管紧张素1-7（1 nM）增加瘦素的分泌和表达，而阿拉曼定（1 nM）减少瘦素的分泌和表达在脂肪组织和分离的脂肪细胞和降低血液瘦素水平在体内。这些作用通过Gq、c-Src、p38丝裂原活化蛋白和IκB活化介导。此外，alamandine通过诱导型一氧化氮合酶和纤溶酶原激活物抑制剂1在脂肪组织和分离的脂肪细胞中的表达诱导一氧化氮的表达。血管紧张素1-7和alamandine对脂肪组织中瘦素的表达和分泌产生相反的作用。该结果表明，脂肪细胞中Mas（血管紧张素1-7受体）和Mas相关G蛋白偶联受体D的作用表现出与血管紧张素II 1型和2型受体类似的相反作用。
Obesity 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. We 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. Angiotensin 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.