Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia.
J Physiol Pharmacol. 2011 Aug;62(4):403-10.
Elevated adiposity is one of the accompanying features of increased age in humans and animals. Angiotensin II (Ang II) is considered as growth promoting peptide to be involved in hypertrophic enlargement of adipose tissue. However, systemic renin-angiotensin system (RAS) seems to decrease with increased age of rats. Local adipose tissue RAS might be independent of the systemic one. Therefore we performed a comprehensive study using rats with increased age from 9 to 26 weeks and evaluated angiotensinogen, angiotensin-converting enzyme (ACE) and AT(1) receptor mRNA in epididymal adipose tissue by RT-PCR. In addition, we determined AT(1) receptor protein by Western blotting and Ang II binding. These RAS parameters were correlated with expression of selected adiposity-dependent proteins such as leptin, adiponectin, insulin-dependent glucose transporter (GLUT4) and PPARgamma. Angiotensinogen and ACE expression decreased with increased age and adiposity. On the contrary, AT(1) receptor mRNA and protein was significantly elevated in 26-week-old rats though the Ang II binding was not different between 9 and 26-week-old animals. These results suggest dynamic adaptation of local adipose tissue RAS components to increased age and adiposity most likely by decreasing local Ang II formation which is thereafter compensated by increased expression of AT(1) receptor. However, this increase in AT(1) receptor mRNA and protein is not reflected in increased receptor binding. We believe that this complex regulation of adipose tissue RAS slows down the negative age and adiposity related changes in adipose tissue leptin, adiponectin, GLUT4 and PPARgamma.
肥胖是人类和动物随年龄增长的伴随特征之一。血管紧张素 II(Ang II)被认为是一种促进生长的肽,参与脂肪组织的肥大增大。然而,系统肾素-血管紧张素系统(RAS)似乎随着大鼠年龄的增加而减少。局部脂肪组织 RAS 可能与系统 RAS 无关。因此,我们使用年龄从 9 周到 26 周的大鼠进行了一项综合研究,并通过 RT-PCR 评估了附睾脂肪组织中的血管紧张素原、血管紧张素转换酶(ACE)和 AT(1)受体 mRNA。此外,我们通过 Western 印迹和 Ang II 结合测定了 AT(1)受体蛋白。这些 RAS 参数与选定的肥胖相关蛋白的表达相关,如瘦素、脂联素、胰岛素依赖性葡萄糖转运体(GLUT4)和 PPARγ。血管紧张素原和 ACE 的表达随年龄和肥胖而降低。相反,AT(1)受体 mRNA 和蛋白在 26 周龄大鼠中显著升高,尽管 9 周龄和 26 周龄动物之间的 Ang II 结合没有差异。这些结果表明,局部脂肪组织 RAS 成分对年龄和肥胖的动态适应很可能通过减少局部 Ang II 的形成来实现,随后通过增加 AT(1)受体的表达来补偿。然而,这种 AT(1)受体 mRNA 和蛋白的增加并没有反映在受体结合的增加上。我们认为,脂肪组织 RAS 的这种复杂调节减缓了脂肪组织瘦素、脂联素、GLUT4 和 PPARγ 与年龄和肥胖相关的负性变化。