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

21 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 (US)
Pages (from-to)359-67
Number of pages9
JournalObesity
Volume24
Issue number2
DOIs
StatePublished - Feb 2016
Externally publishedYes

Keywords

  • Adipose Tissue/metabolism
  • Adipose Tissue, White/metabolism
  • Angiotensinogen/metabolism
  • Animals
  • Inflammation/metabolism
  • Macrophages/metabolism
  • Mice
  • Mice, Knockout

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