Lack of weight gain after angiotensin AT1 receptor blockade in diet-induced obesity is partly mediated by an angiotensin-(1-7)/Mas-dependent pathway

Item Type:	Article
Title:	Lack of weight gain after angiotensin AT1 receptor blockade in diet-induced obesity is partly mediated by an angiotensin-(1-7)/Mas-dependent pathway
Creators Name:	Schuchard, J. and Winkler, M. and Stölting, I. and Schuster, F. and Vogt, F.M. and Barkhausen, J. and Thorns, C. and Santos, R.A. and Bader, M. and Raasch, W.
Abstract:	BACKGROUND AND PURPOSE: Angiotensin AT1 receptor antagonists induce weight loss; however, the mechanism underlying this phenomenon is unknown. The Mas receptor agonist angiotensin-(1-7) is a metabolite of angiotensin I and of angiotensin II . As an agonist of Mas receptors, angiotensin-(1-7) has beneficial cardiovascular and metabolic effects. EXPERIMENTAL APPROACH: We investigated the anti-obesity effects of transgenically overexpressed angiotensin-(1-7) in rats. We secondly examined whether weight loss due to telmisartan (8 mg.kg(-1) .d(-1) ) in diet-induced obese Sprague Dawley (SD) rats can be blocked when the animals were co-treated with the Mas receptor antagonist A779 (24 or 72 mug.kg(-1) .d(-1) ). KEY RESULTS: In contrast to wild-type controls, transgenic rats overexpressing angiotensin-(1-7) had 1.) diminished body weight when they were regularly fed with chow; 2.) were protected from developing obesity although they were fed with cafeteria diet (CD); 3.) showed a reduced energy intake that was mainly related to a lower CD intake; 5.) remained responsive to leptin despite chronic CD feeding; 6.) had a higher, strain-dependent energy expenditure, and 7.) were protected from developing insulin resistance despite CD feeding. Telmisartan-induced weight loss in SD rats was partially antagonized after a high, but not a low dose of A779. CONCLUSIONS AND IMPLICATIONS: Angiotensin-(1-7) regulated food intake and body weight and contributed to the weight loss after AT1 receptor blockade. Angiotensin-(1-7)-like agonists may be drug candidates for treating obesity.
Keywords:	Angiotensin I, Angiotensin II, Angiotensin II Type 1 Receptor Blockers, Benzimidazoles, Benzoates, Diet, Energy Intake, Energy Metabolism, Genetically Modified Animals, G-Protein-Coupled Receptors, Insulin Resistance, Leptin, Obesity, Peptide Fragments, Proto-Oncogene Proteins, Signal Transduction, Weight Gain, Weight Loss, Animals, Rats
Source:	British Journal of Pharmacology
ISSN:	0007-1188
Publisher:	Wiley-Blackwell
Volume:	172
Number:	15
Page Range:	3764-3778
Date:	August 2015
Official Publication:	https://doi.org/10.1111/bph.13172
PubMed:	View item in PubMed

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