Angiotensinogen gene silencing reduces markers of lipid accumulation and inflammation in cultured adipocytes.
Angiotensinogen gene silencing reduces markers of lipid accumulation and inflammation in cultured adipocytes.
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DOI：
10.3389/fendo.2013.00010
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发表时间：
2013
影响因子：
5.2
通讯作者：
Moustaid-Moussa N
中科院分区：
文献类型：
--
作者：
Carroll WX;Kalupahana NS;Booker SL;Siriwardhana N;Lemieux M;Saxton AM;Moustaid-Moussa N
脂肪组织分泌的炎性脂肪因子是肥胖相关炎症和其他代谢功能障碍的主要贡献者。我们和其他人最近已经证实了脂肪组织中的肾素-血管紧张素系统在肥胖、炎症和胰岛素抵抗的发病机制中的作用。我们假设脂肪细胞来源的血管紧张素原（Agt）在脂肪生成和/或脂肪生成以及炎症中起着关键作用。这使用3 T3-L1脂肪细胞进行测试，所述脂肪细胞用Agt-shRNA或乱序Sc-shRNA稳定转染作为对照。将转染的前脂肪细胞分化，并通过微阵列和PCR分析以及脂肪因子分析来研究脂肪Agt的作用。正如预期的那样，Agt基因沉默显著降低了Agt及其激素产物血管紧张素II（Ang II）的表达，以及3 T3-L1脂肪细胞中的脂质积累。基因芯片研究发现了一些参与脂质代谢和炎症通路的基因，这些基因被Agt基因失活下调，如甘油-3-磷酸脱氢酶1（Gpd 1）、血清淀粉样蛋白A3（Saa 3）、核苷酸结合寡聚化结构域1（Nod 1）和信号转导和转录激活因子1（Stat 1）。小鼠脂肪生成PCR阵列显示脂肪生成/脂肪生成基因的表达水平较低，如过氧化物酶体增殖物激活受体γ（PPARγ）、固醇调节元件结合转录因子1（Srebf 1）、脂肪生成素（Adig）和脂肪酸结合蛋白4（Fabp 4）。此外，Agt基因的沉默显著降低了促炎性脂肪因子的表达，包括白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和单核细胞趋化蛋白-1（MCP-1）。总之，本研究直接证明了Agt在脂肪细胞代谢和炎症中的关键作用，并进一步支持脂肪Agt在肥胖相关代谢改变的发病机制中的潜在作用。
Inflammatory adipokines secreted from adipose tissue are major contributors to obesity-associated inflammation and other metabolic dysfunctions. We and others have recently documented the contribution of adipose tissue renin-angiotensin system to the pathogenesis of obesity, inflammation, and insulin resistance. We hypothesized that adipocyte-derived angiotensinogen (Agt) plays a critical role in adipogenesis and/or lipogenesis as well as inflammation. This was tested using 3T3-L1 adipocytes, stably transfected with Agt-shRNA or scrambled Sc-shRNA as a control. Transfected preadipocytes were differentiated and used to investigate the role of adipose Agt through microarray and PCR analyses and adipokine profiling. As expected, Agt gene silencing significantly reduced the expression of Agt and its hormone product angiotensin II (Ang II), as well as lipid accumulation in 3T3-L1 adipocytes. Microarray studies identified several genes involved in lipid metabolism and inflammatory pathways which were down-regulated by Agt gene inactivation, such as glycerol-3-phosphate dehydrogenase 1 (Gpd1), serum amyloid A 3 (Saa3), nucleotide-binding oligomerization domain containing 1 (Nod1), and signal transducer and activator of transcription 1 (Stat1). Mouse adipogenesis PCR arrays revealed lower expression levels of adipogenic/lipogenic genes such as peroxisome proliferator activated receptor gamma (PPARγ), sterol regulatory element binding transcription factor 1 (Srebf1), adipogenin (Adig), and fatty acid binding protein 4 (Fabp4). Further, silencing of Agt gene significantly lowered expression of pro-inflammatory adipokines including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and monocyte chemotactic protein-1 (MCP-1). In conclusion, this study directly demonstrates critical effects of Agt in adipocyte metabolism and inflammation and further support a potential role for adipose Agt in the pathogenesis of obesity-associated metabolic alterations.