title: Inactivation of adipose angiotensinogen reduces adipose tissue macrophages and increases metabolic activity.
abstract: OBJECTIVE
  The adipose renin-angiotensin system (RAS) has been linked to obesity-induced inflammation, though mechanisms are not completely understood. In this study, adipose-specific angiotensinogen knockout mice (Agt-KO) were generated to determine whether Agt inactivation reduces inflammation and alters the metabolic profile of the Agt-KO mice compared to wild-type (WT) littermates.
  
  
  METHODS
  Adipose tissue-specific Agt-KO mice were created using the Cre-LoxP system with both Agt-KO and WT littermates fed either a low-fat or high-fat diet to assess metabolic changes. White adipose tissue was used for gene/protein expression analyses and WAT stromal vascular cells for metabolic extracellular flux assays.
  
  
  RESULTS
  No significant differences were observed in body weight or fat mass between both genotypes on either diet. However, improved glucose clearance was observed in Agt-KO compared to WT littermates, consistent with higher expression of genes involved in insulin signaling, glucose transport, and fatty acid metabolism. Furthermore, Agt inactivation reduced total macrophage infiltration in Agt-KO mice fed both diets. Lastly, stroma vascular cells from Agt-KO mice revealed higher metabolic activity compared to WT mice.
  
  
  CONCLUSIONS
  These findings indicate that adipose-specific Agt inactivation leads to reduced adipose inflammation and increased glucose tolerance mediated in part via increased metabolic activity of adipose cells.
authors.affiliation: Department of Nutritional Sciences, Texas Tech University, Lubbock, Texas, USA.
authors.forename: Monique J
authors.initials: MJ
authors.lastname: LeMieux
authors.affiliation: Department of Nutritional Sciences, Texas Tech University, Lubbock, Texas, USA.
authors.forename: Latha
authors.initials: L
authors.lastname: Ramalingam
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
authors.forename: Randall L
authors.initials: RL
authors.lastname: Mynatt
authors.affiliation: Department of Nutritional Sciences, Texas Tech University, Lubbock, Texas, USA.|Department of Physiology, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka.
authors.forename: Nishan S
authors.initials: NS
authors.lastname: Kalupahana
authors.affiliation: Department of Pharmacology, Physiology and Toxicology, School of Medicine, Marshall University, Huntington, West Virginia, USA.
authors.forename: Jung Han
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Nutritional Sciences, Texas Tech University, Lubbock, Texas, USA.
authors.forename: Naïma
authors.initials: N
authors.lastname: Moustaïd-Moussa
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000378:metabolism; D000808:Angiotensinogen / Q000378:metabolism*; D000818:Animals; D007249:Inflammation / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout
chemical_list: D000808:Angiotensinogen