Premium
Role of the Angiotensin AT 2 receptor in obesity‐linked inflammation and renal injury: Effect of gender
Author(s) -
Dhande Isha,
Khan Mohammed Azhar,
Nag Sourashish,
Hussain Tahir
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1114.2
Subject(s) - medicine , endocrinology , inflammation , obesity , tumor necrosis factor alpha , angiotensin ii , receptor , kidney
The Angiotensin AT 2 receptor (AT 2 R) is up‐regulated in response to tissue injury and is implicated in tissue protection and repair. We have recently demonstrated that the AT 2 R signaling may be differentially regulated in males and females in the setting of obesity. The present study was designed to investigate the effect of gender on the protective role of the AT 2 R in mediating obesity‐linked renal inflammation and injury. Young, 3–4 week old male and female AT 2 R‐deficient (AT 2 KO) mice were maintained on a normal (ND) or high‐fat diet (HFD) for 16 weeks. Female, but not male, AT 2 KO ND mice had 5‐fold higher levels of plasma and renal tumor necrosis factor‐α (TNF‐α). HFD significantly increased (Male: 4‐fold and Female: 5‐fold higher compared to ND controls) plasma and renal levels of TNF‐α. AT 2 KO males and females on HFD had 1.5‐fold higher TNF‐α compared to HFD controls. Renal histology revealed increased mesangial matrix expansion (MME) in all the HFD groups (both, control and AT 2 KO), while the glomeruli of the ND control and AT 2 KO male mice were normal. On the other hand, female AT 2 KO mice even on ND had greater extent of MME compared to controls (1.1±0.2 vs 0.3±0.1) and HFD further increased MME (2.9±0.1 vs 1.3±0.2). Our results suggest that AT 2 R is reno‐protective in obesity‐linked renal inflammation and injury. Further, the protective role of the AT 2 R appears to be more critical in females. Supported by NIH R01 DK‐61578.