title: 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.affiliation: Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, KY 40536-0200, USA.
authors.forename: Frederique
authors.initials: F
authors.lastname: Yiannikouris
authors.forename: Manisha
authors.initials: M
authors.lastname: Gupte
authors.forename: Kelly
authors.initials: K
authors.lastname: Putnam
authors.forename: Sean
authors.initials: S
authors.lastname: Thatcher
authors.forename: Richard
authors.initials: R
authors.lastname: Charnigo
authors.forename: Debra L
authors.initials: DL
authors.lastname: Rateri
authors.forename: Alan
authors.initials: A
authors.lastname: Daugherty
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Cassis
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism; D000808:Angiotensinogen / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D004032:Diet; D006339:Heart Rate / Q000502:physiology; D006973:Hypertension / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009765:Obesity / Q000150:complications* / Q000235:genetics / Q000378:metabolism
chemical_list: D000808:Angiotensinogen