Angiotensinogen gene silencing in adipocytes reduces markers of inflammation and lipid accumulation

Abstract

Angiotensinogen (Agt), the only known precursor for the hypertensive hormone Angiotensin II (Ang II), is expressed in adipose tissue. Studies from our laboratory and others have provided evidence linking adipocyte‐derived Agt to obesity, inflammation and insulin resistance. To further determine the direct contribution of adipose Agt to these disorders, we generated 3T3‐L1 cells stably transfected with Agt‐shRNA or scrambled‐shRNA sequences, to determine changes in metabolic and inflammatory markers as well as global transcriptional alterations caused by Agt silencing. Adipocytes lacking Agt exhibited significantly reduced levels of Ang II, triglycerides and lipogenic gene expression, consistent with decreased PPAR‐γ activity. Knockdown of the Agt gene also downregulated several adipose tissue inflammatory markers including IL6, TNF‐α and MCP‐1. Furthermore, microarray and qRT‐PCR analyses revealed several candidate genes involved in lipid metabolism and inflammatory pathways, which were differentially regulated by Agt; these included NOD1, a novel Pattern Recognition Receptor, the acute phase protein SAA3, the transcription factor STAT1 and the chemokine CXCL12, all of which were down regulated by Agt silencing. In conclusion, our findings suggest that adipose Agt plays a critical role in adipose tissue expansion and the associated inflammation and metabolic complications.Grant Funding Source: UT Obesity Research Center and TN AgResearch