Adipocyte Deficiency of Angiotensinogen Prevents Obesity-Induced Hypertension in Male Mice
Previous studies demonstrated that diet-induced obesity increased plasma angiotensin II concentrations and elevated systolic blood pressures in male mice. Adipocytes express angiotensinogen and secrete angiotensin peptides. We hypothesize that adipocyte-derived angiotensin II mediates obesity-induced increases in systolic blood pressure in male high fat-fed C57BL/6 mice. Systolic blood pressure was measured by radiotelemetry during week 16 of low-fat or high-fat feeding in Agtfl/fl and adipocyte angiotensinogen-deficient mice (AgtaP2). Adipocyte angiotensinogen deficiency had no effect on diet-induced obesity. Basal 24-hour systolic blood pressure was not different in low fat-fed Agtfl/fl compared with AgtaP2 mice (124±3 versus 128±3 mm Hg, respectively). In Agtfl/fl mice, high-fat feeding significantly increased systolic blood pressure (24 hours; 134±2 mm Hg; P<0.05). In contrast, high fat-fed AgtaP2 mice did not exhibit an increase in systolic blood pressure (126±2 mm Hg). Plasma angiotensin II concentrations were increased by high-fat feeding in Agtfl/fl mice (low fat, 32±14; high fat, 219±58 pg/mL; P<0.05). In contrast, high fat-fed AgtaP2 mice did not exhibit elevated plasma angiotensin II concentrations (high fat, 18±7 pg/mL). Similarly, adipose tissue concentrations of angiotensin II were significantly decreased in low fat- and high fat-fed AgtaP2 mice compared with controls. In conclusion, adipocyte angiotensinogen deficiency prevented high fat-induced elevations in plasma angiotensin II concentrations and systolic blood pressure. These results suggest that adipose tissue serves as a major source of angiotensin II in the development of obesity hypertension.
- Received February 6, 2012.
- Revision received February 27, 2012.
- Accepted September 24, 2012.
- © 2012 American Heart Association, Inc.