Angiotensin II increases adipose angiotensinogen expression
Angiotensin II increases adipose angiotensinogen expression
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DOI：
10.1152/ajpendo.00277.2006
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发表时间：
2007-05-01
影响因子：
5.1
通讯作者：
Cassis, Lisa A.
中科院分区：
文献类型：
--
作者：
Lu, Hong;Boustany-Kari, Carine M.;Cassis, Lisa A.
除了肝脏明确的作用外，脂肪组织已被确认为血管紧张素原（AGT）的一个重要来源。本研究的目的是确定参与脂肪组织中AGT调节的血管紧张素II（ANG II）受体，以及这种调节与全身性AGT和/或血管紧张素肽浓度的关系。在低密度脂蛋白受体缺陷（LDLR - / -）雄性小鼠中，脂肪组织中AGT的mRNA丰度是肝脏中的68%，血管紧张素1a型（AT(1a)）受体（AT(1a)R）的脂肪组织mRNA丰度是肝脏中的38%，而血管紧张素2型（AT(2)）受体（AT(2)R）的mRNA丰度在脂肪组织中比肝脏高57%。在AT(1a)R缺陷（AT(1a)R - / -）小鼠的血浆中，AGT和血管紧张素肽浓度降低，同时肝脏中AGT表达也降低。相比之下，在AT(1a)R - / -小鼠中脂肪组织的AGT mRNA丰度未改变。AT(2)R - / -小鼠表现出血浆血管紧张素肽浓度升高，以及脂肪组织中AGT和AT1aR mRNA丰度显著升高。氯沙坦可消除AT(2)R - / -小鼠中脂肪组织AGT mRNA丰度的增加。相反，在AT(2)R - / -小鼠中肝脏的AGT和AT1aR mRNA丰度未改变。向LDLR - / -小鼠持续输注ANG II 28天，可显著增加脂肪组织中AGT和AT1aR的mRNA，但不改变肝脏中AGT和AT1aR的mRNA。这些结果表明，脂肪组织与肝脏中AT(1a)/AT(2)受体mRNA丰度的差异有助于组织特异性的ANG II介导的AGT调节。ANG II的长期输注强烈刺激脂肪组织中AT1aR和AGT的mRNA丰度，这表明脂肪组织是激活的全身性肾素 - 血管紧张素系统的主要贡献者。
In addition to the well-defined contribution of the liver, adipose tissue has been recognized as an important source of angiotensinogen (AGT). The purpose of this study was to define the angiotensin II (ANG II) receptors involved in regulation of adipose AGT and the relationship of this control to systemic AGT and/or angiotensin peptide concentrations. In LDL receptor-deficient (LDLR-/-) male mice, adipose mRNA abundance of AGT was 68% of that in liver, and adipose mRNA abundance of the angiotensin type 1a (AT(1a)) receptor (AT(1a)R) was 38% of that in liver, whereas mRNA abundance of the angiotensin type 2 (AT(2)) receptor (AT(2)R) was 57% greater in adipose tissue than in liver. AGT and angiotensin peptide concentrations were decreased in plasma of AT(1a)R-deficient (AT(1a)R(-/-)) mice and were paralleled by reductions in AGT expression in liver. In contrast, adipose AGT mRNA abundance was unaltered in AT(1a)R(-/-) mice. AT(2)R(-/-) mice exhibited elevated plasma angiotensin peptide concentrations and marked elevations in adipose AGT and AT1aR mRNA abundance. Increases in adipose AGT mRNA abundance in AT(2)R(-/-) mice were abolished by losartan. In contrast, liver AGT and AT1aR mRNA abundance were unaltered in AT(2)R(-/-) mice. Infusion of ANG II for 28 days into LDLR-/- mice markedly increased adipose AGT and AT1aR mRNA but did not alter liver AGT and AT1aR mRNA. These results demonstrate that differential mRNA abundance of AT(1a)/AT(2) receptors in adipose tissue vs. liver contributes to tissue-specific ANG II-mediated regulation of AGT. Chronic infusion of ANG II robustly stimulated AT1aR and AGT mRNA abundance in adipose tissue, suggesting that adipose tissue serves as a primary contributor to the activated systemic renin-angiotensin system.