Comparative Expression of Renin-Angiotensin Pathway Proteins in Visceral Versus Subcutaneous Fat.
Comparative Expression of Renin-Angiotensin Pathway Proteins in Visceral Versus Subcutaneous Fat.
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DOI：
10.3389/fphys.2018.01370
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发表时间：
2018
影响因子：
4
通讯作者：
Singh P
中科院分区：
文献类型：
--
作者：
Zhang Y;Somers KR;Becari C;Polonis K;Pfeifer MA;Allen AM;Kellogg TA;Covassin N;Singh P
体脂分布导致肥胖相关的代谢和心血管疾病。内脏脂肪比皮下脂肪更有害。然而，内脏脂肪介导的心脏代谢失调的机制尚不完全清楚。脂肪组织(AT)中肾素血管紧张素系统(RAS)表达的局限性增加可能与此有关。因此，我们使用来自手术患者的配对样本(N=20，体重指数：45.6±6.2 kg/m2，年龄：44.6±9.1岁)，研究了内脏和皮下AT中RAS组分的mRNA和蛋白表达。我们还检测了肾素-血管紧张素-醛固酮系统(RAAS)靶向药物(N=10，体重指数：47.2±9.3 kg/m2，年龄：53.3±10.1岁)患者的AT中RAS相关蛋白。皮下和内脏AT的蛋白质表达比较显示，内脏AT的肾素表达增加(p=0.004)，血管紧张素原的表达没有变化(p=0.987)。在参与血管紧张素生成的蛋白质中，血管紧张素转换酶在皮下血管紧张素转换酶(P=0.02)中升高，而在内脏脂肪中血管紧张素转换酶(P=0.001)和血管紧张素转换酶-2(P=0.001)升高。此外，血管紧张素Ⅱ2型受体(p=0.007)和血管紧张素Ⅱ1型受体(p=0.031)的内脏脂肪表达较高，而Mas受体(p<；0.001)的表达较低。在两个储存库中，磷酸化P53(p=0.147)、AT纤维化(p=0.138)和平均脂肪细胞大小(p=0.846)相似。然而，内脏AT显示炎症(肿瘤坏死因子α，p<；0.001；IL-6，p=0.001)和氧化应激标志物(NOX2，p=0.038；NOX4，p<；0.001)的基因表达增加。值得注意的是，服用和不服用RAAS相关药物的受试者中，RAS组分的mRNA和蛋白表达没有差异。综上所述，一些RAS相关蛋白在皮下和内脏AT中的表达存在差异。这种差异表达可能不会改变Angii，但可能会增加内脏脂肪中Ang1-7的生成。这两个部位活性血管紧张素肽和受体表达的潜在差异表明，局部RAS可能不参与肥胖者内脏和皮下AT功能的差异。我们的发现不支持局部RAS差异在内脏脂肪介导的心血管和代谢病理发展中的作用。
Body fat distribution contributes to obesity-related metabolic and cardiovascular disorders. Visceral fat is more detrimental than subcutaneous fat. However, the mechanisms underlying visceral fat-mediated cardiometabolic dysregulation are not completely understood. Localized increases in expression of the renin angiotensin system (RAS) in adipose tissue (AT) may be implicated. We therefore investigated mRNA and protein expression of RAS components in visceral versus subcutaneous AT using paired samples from individuals undergoing surgery (N = 20, body mass index: 45.6 ± 6.2 kg/m2, and age: 44.6 ± 9.1 years). We also examined RAS-related proteins in AT obtained from individuals on renin angiotensin aldosterone system (RAAS) targeted drugs (N = 10, body mass index: 47.2 ± 9.3 kg/m2, and age: 53.3 ± 10.1 years). Comparison of protein expression between subcutaneous and visceral AT samples showed an increase in renin (p = 0.004) and no change in angiotensinogen (p = 0.987) expression in visceral AT. Among proteins involved in angiotensin peptide generation, angiotensin converting enzyme (p = 0.02) was increased in subcutaneous AT while chymase (p = 0.001) and angiotensin converting enzyme-2 (p = 0.001) were elevated in visceral fat. Furthermore, visceral fat expression of angiotensin II type-2 receptor (p = 0.007) and angiotensin II type-1 receptor (p = 0.031) was higher, and MAS receptor (p < 0.001) was lower. Phosphorylated-p53 (p = 0.147), AT fibrosis (p = 0.138) and average adipocyte size (p = 0.846) were similar in the two depots. Nonetheless, visceral AT showed increased mRNA expression of inflammatory (TNFα, p < 0.001; IL-6, p = 0.001) and oxidative stress markers (NOX2, p = 0.038; NOX4, p < 0.001). Of note, mRNA and protein expression of RAS components did not differ between subjects taking or not taking RAAS related drugs. In summary, several RAS related proteins are differentially expressed in subcutaneous versus visceral AT. This differential expression may not alter AngII but likely increases Ang1-7 generation in visceral fat. These potential differences in active angiotensin peptides and receptor expression in the two depots suggest that localized RAS may not be involved in differences in visceral vs subcutaneous AT function in obese individuals. Our findings do not support a role for localized RAS differences in visceral fat-mediated development of cardiovascular and metabolic pathology.
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