The Adipose Renin‐Angiotensin System Modulates Systemic Markers of Insulin Sensitivity and Activates the Intrarenal Renin‐Angiotensin System

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Abstract
Background. The adipose tissue renin‐angiotensin system (RAS) contributes to regulation of fat mass and may also impact systemic functions such as blood pressure and metabolism. Methods and results. A panel of mouse models including mice lacking angiotensinogen, Agt (Agt‐KO), mice expressing Agt solely in adipose tissue (aP2‐Agt/Agt‐KO), and mice overexpressing Agt in adipose tissue (aP2‐Agt) was studied. Total body weight, epididymal fat pad weight, and circulating levels of leptin, insulin, and resistin were significantly decreased in Agt‐KO mice, while plasma adiponectin levels were increased. aP2‐Agt mice exhibited increased adiposity and plasma leptin and insulin levels compared to wild type (WT) controls. Angiotensinogen and type I Ang II receptor protein levels were also elevated in kidney of aP2‐Agt mice. Conclusion. These findings demonstrate that alterations in adipose RAS activity significantly impact both local and systemic physiology in a way that may contribute to the detrimental health effects of obesity.
Funding Information
  • U.S. Department of Energy (DE-AC05-00OR22725)