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Obesity‐induced hypertension is associated with increases in adipose tissue‐derived angiotensinogen in female mice exposed to early life stress (ELS).
Author(s) -
Herald Joseph,
Murphy Margaret,
Cohn Dianne,
Loria Analia
Publication year - 2017
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.31.1_supplement.852.2
Subject(s) - medicine , adipose tissue , endocrinology , weaning , angiotensin ii , renin–angiotensin system , obesity , angiotensin ii receptor type 1 , receptor , kidney , biology , chemistry , blood pressure
ELS is an established independent risk factor for cardiovascular disease. We use Maternal separation and early weaning (MSEW) during postnatal life as a mouse model of ELS. Previously, we have shown that MSEW exacerbates the development of obesity‐induced hypertension (HT) in female mice. Given the well‐known role of renin‐angiotensin system (RAS) during the development of obesity‐induced HT, the goal of this study was to determine the RAS status in female MSEW mice. MSEW was performed in C57BL/6 mice from postnatal days 2–16. Undisturbed litters served as control group (C). Mice were placed on a low‐fat diet (LFD, 10% kcal from fat) or HFD (60% kcal from fat) for 16 weeks upon weaning. Plasma renin concentration (PRC) was reduced in female MSEW compared with C (p<0.05), suggesting increased circulating AngII levels. Angiotensinogen (AGT) protein level, the only known precursor for angiotensin peptides, showed similar levels between groups in plasma (6.2±0.3 vs. 5.5±0.1 ug/ml, p<0.05) and liver (1.6±0.2 vs. 1.7±0.3 ng/ml/g tissue); however, adipose tissue and media explants displayed increased AGT secretion in female MSEW mice compared with C (29±9 vs. 98±8 and 15±1 vs. 22±2 ng/ml/g tissue, respectively, p<0.05). AngII receptor subtypes 1 and 2 (AT1 and AT2) were not different between groups in liver, adipose tissue, brain and kidney. In additional studies, we found increased adipose tissue‐derived AGT in media explants from female MSEW after one week on HFD (27±2 vs. 46±3 ng/ml/g tissue, p<0.05). Finally, AGT mRNA expression in visceral fat was increased in MSEW pups at postnatal day 7 (p<0.05). Taken together, these data indicate that adipose tissue‐derived AGT is particularly susceptible to MSEW and may serve as a major source of circulating angiotensin II peptide in MSEW mice thereby contributing to obesity‐induced HT. Support or Funding Information HL111354