Inactivation of adipose angiotensinogen reduces adipose tissue macrophages and increases metabolic activity

Monique J. LeMieux, Latha Ramalingam, Randall L. Mynatt, Nishan S. Kalupahana, Jung Han Kim, Naïma Moustaïd-Moussa

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

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.

Original languageEnglish
Pages (from-to)359-367
Number of pages9
JournalObesity
Volume24
Issue number2
DOIs
StatePublished - Feb 1 2016

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