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 language | English (US) |
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Pages (from-to) | 359-67 |
Number of pages | 9 |
Journal | Obesity |
Volume | 24 |
Issue number | 2 |
DOIs | |
State | Published - Feb 2016 |
Externally published | Yes |
Keywords
- Adipose Tissue/metabolism
- Adipose Tissue, White/metabolism
- Angiotensinogen/metabolism
- Animals
- Inflammation/metabolism
- Macrophages/metabolism
- Mice
- Mice, Knockout