Abstract 11703: Adipose Angiotensinogen Inactivation Reduces Adipose Tissue Inflammation and Increases Metabolic Activity in Adipose Stroma Vascular cells
The adipose renin-angiotensin system (RAS) is an important regulator of blood pressure and fluid balance and has been linked to obesity-induced inflammation, though mechanisms are not completely understood. Previously, we showed that overexpression of the RAS protein precursor, angiotensinogen (Agt) in adipose tissue increases adiposity, insulin resistance, adipose and systemic inflammation in mice fed a low-fat diet (LFD). Accordingly, we hypothesized that Agt inactivation in adipose tissue will protect against obesity-associated inflammation. To test this hypothesis, we generated adipose tissue Agt knockout (Agt-KO) mice using the aP2-Cre-LoxP system. Agt-KO and wild-type (WT) littermates were each fed a LFD or high-fat diet (HFD) to assess metabolic changes. Our results demonstrate that while no significant differences were observed in body weight or fat mass between the two genotypes on either diet, glucose tolerance was improved in the Agt-KO compared to the WT littermates. This was consistent with higher expression of genes involved in insulin signaling, glucose transport and fatty acid metabolism in white adipose tissue from Agt-KO mice. Moreover, Agt inactivation reduced total adipose macrophage infiltration,and gene/protein expression of MCP-1 and other proinflammatory adipokines in Agt-KO mice compared to WT. Lastly, extracellular flux analyses (using Seahorse Xfe) in both differentiated and non-differentiated stromal vascular cells revealed higher glycolytic activity and mitochondrial respiration in Agt-KO compared to WT mice. Overall, our findings indicate that adipose Agt inactivation reduced adipose inflammation and improved glucose tolerance in part via increased metabolic activity of adipose cells. The cellular and molecular changes observed are consistent with previously reported functions of RAS in insulin resistance, and inflammation.
Funded by a GIA from the American Heart Association Southwest Affiliate (NMM)
Author Disclosures: M.J. LeMieux: None. L. Ramalingam: None. R. Mynatt: None. N.S. Kalupahana: None. J. Kim: None. N. Moustaid-Moussa: None.
- © 2015 by American Heart Association, Inc.