Adipocyte deficiency of angiotensinogen prevents obesity-induced hypertension in male mice.

Abstract

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 Agt(fl/fl) and adipocyte angiotensinogen-deficient mice (Agt(aP2)). Adipocyte angiotensinogen deficiency had no effect on diet-induced obesity. Basal 24-hour systolic blood pressure was not different in low fat-fed Agt(fl/fl) compared with Agt(aP2) mice (124 ± 3 versus 128 ± 3 mm Hg, respectively). In Agt(fl/fl) mice, high-fat feeding significantly increased systolic blood pressure (24 hours; 134 ± 2 mm Hg; P<0.05). In contrast, high fat-fed Agt(aP2) 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 Agt(fl/fl) mice (low fat, 32 ± 14; high fat, 219 ± 58 pg/mL; P<0.05). In contrast, high fat-fed Agt(aP2) 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 Agt(aP2) 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.

• Authors: Frederique Yiannikouris, Manisha Gupte, Kelly Putnam, Sean Thatcher, Richard Charnigo, Debra L Rateri, Alan Daugherty, Lisa A Cassis
• Journal: Hypertension (Dallas, Tex. : 1979) (Hypertension) Vol. 60 Issue 6 Pg. 1524-30 (Dec 2012) ISSN: 1524-4563 [Electronic] United States
• PMID: 23108647 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Angiotensinogen

Topics

• Adipocytes (metabolism)
• Adipose Tissue (metabolism)
• Angiotensinogen (genetics, metabolism)
• Animals
• Blood Pressure (physiology)
• Diet
• Heart Rate (physiology)
• Hypertension (etiology, genetics, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Obesity (complications, genetics, metabolism)