Abstract
Abstract 015: Regulation of Resting Metabolism by the Angiotensin AT2 Receptor
Hypertension (Dallas, Tex. 1979), Vol.64(Suppl_1 Suppl 1), pp.A015-A015
11/2014
DOI: 10.1161/hyp.64.suppl_1.015
Abstract
The renin-angiotensin system (RAS) positively correlates with obesity, and contributes to energy homeostasis through opposing actions in the brain and adipose. We hypothesize that site- and receptor-specific modulation may represent a novel therapeutic target for obesity. Transgenic “sRA” mice exhibit brain-specific RAS hyperactivity through expression of human renin in neurons (synapsin promoter) and human angiotensinogen via its own promoter. Previously we documented that sRA mice exhibit a suppressed circulating RAS, and an elevated resting metabolic rate (RMR) that is sensitive to replacement of circulating angiotensin II or the AT2 receptor (AT2R) agonist, CGP-42112a (CGP, 100 ng/kg/min, s.c.). sRA mice consume more food than littermate controls (con n=7, 12.98±0.65 vs sRA n=8, 15.41±0.70 g/d, P<0.05), but because of a major suppression of digestive efficiency (con 77.6±2.3 vs sRA 59.3±4.7 % consumed, P<0.05), sRA mice absorb a normal number of calories (con 10.04±0.50 vs sRA 9.07±0.76 kcal/d). Chronic CGP had no effect on total daily caloric absorption (con+CGP n=7, 9.83±0.95 vs sRA+CGP n=5, 9.32±0.80 kcal/d); however CGP appears to disproportionately increase weight gain in sRA mice (vehicle +0.33±0.49 vs CGP +1.54±0.47 g/8 wks, P=0.27) compared to control mice (vehicle +2.12±1.00 vs CGP +2.47±0.73 g/8 wks, P=0.73), consistent with a suppression of energy expenditure by CGP. Given the increased RMR and core temperature in sRA mice, we next examined the expression of uncoupling protein-1 (UCP1) content of thermogenic adipose tissues by Western blot (all n=3, vs perilipin). Interscapular brown adipose tissue UCP1 was unchanged in sRA mice (94±6%), and weakly suppressed by CGP treatment (84±4% of sRA). Inguinal adipose UCP1 was increased in sRA mice (198±13%), and this was suppressed by CGP treatment (72±9% of sRA). UCP1 mRNA levels paralleled protein in both fat types. Cultured adipocytes from 4 day old AT2-deficient mice exhibited increased UCP1 protein vs littermate controls (190%). Further, CGP (10 nM) reduced UCP1 in control adipocytes (by 30%). These data support a suppressive action of AT2R upon RMR most likely through UCP1. Inguinal adipose AT2R may therefore contribute to obesity through suppression of RMR.
Details
- Title: Subtitle
- Abstract 015: Regulation of Resting Metabolism by the Angiotensin AT2 Receptor
- Creators
- Nicole Littlejohn - Univ of Iowa, Iowa City, IABenjamin WeidemannNicole PearsonKathleen MarkanMatthew PotthoffCurt SigmundJustin Grobe
- Resource Type
- Abstract
- Publication Details
- Hypertension (Dallas, Tex. 1979), Vol.64(Suppl_1 Suppl 1), pp.A015-A015
- Publisher
- American Heart Association, Inc
- DOI
- 10.1161/hyp.64.suppl_1.015
- ISSN
- 0194-911X
- eISSN
- 1524-4563
- Language
- English
- Date published
- 11/2014
- Academic Unit
- Neuroscience and Pharmacology; Iowa Neuroscience Institute; Molecular Physiology and Biophysics
- Record Identifier
- 9984071958502771
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