title: Adipocyte-specific deficiency of angiotensinogen decreases plasma angiotensinogen concentration and systolic blood pressure in mice.
abstract: Previous studies demonstrated that overexpression of angiotensinogen (AGT) in adipose tissue increased blood pressure. However, the contribution of endogenous AGT in adipocytes to the systemic renin-angiotensin system (RAS) and blood pressure control is undefined. To define a role of adipocyte-derived AGT, mice with loxP sites flanking exon 2 of the AGT gene (Agt(fl/fl)) were bred to transgenic mice expressing Cre recombinase under the control of an adipocyte fatty acid-binding protein 4 promoter (aP2) promoter to generate mice with adipocyte AGT deficiency (Agt(aP2)). AGT mRNA abundance in adipose tissue and AGT secretion from adipocytes were reduced markedly in adipose tissues of Agt(aP2) mice. To determine the contribution of adipocyte-derived AGT to the systemic RAS and blood pressure control, mice were fed normal laboratory diet for 2 or 12 mo. In males and females of each genotype, body weight and fat mass increased with age. However, there was no effect of adipocyte AGT deficiency on body weight, fat mass, or adipocyte size. At 2 and 12 mo of age, mice with deficiency of AGT in adipocytes had reduced plasma concentrations of AGT (by 24-28%) compared with controls. Moreover, mice lacking AGT in adipocytes exhibited reduced systolic blood pressures compared with controls (Agt(fl/fl), 117 ± 2; Agt(aP2), 110 ± 2 mmHg; P < 0.05). These results demonstrate that adipocyte-derived AGT contributes to the systemic RAS and blood pressure control.
authors.affiliation: Graduate Center for Nutritional Sciences, Univ. of Kentucky, Lexington, KY 40536-0200, USA.
authors.forename: Frederique
authors.initials: F
authors.lastname: Yiannikouris
authors.forename: Michael
authors.initials: M
authors.lastname: Karounos
authors.forename: Richard
authors.initials: R
authors.lastname: Charnigo
authors.forename: Victoria L
authors.initials: VL
authors.lastname: English
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*; D050154:Adiposity / Q000502:physiology; D000808:Angiotensinogen / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology*; D001835:Body Weight / Q000502:physiology; D005260:Female; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D012084:Renin-Angiotensin System / Q000502:physiology*
chemical_list: D001786:Blood Glucose; D000808:Angiotensinogen
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