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Br J Pharmacol. 2015 Aug;172(15):3764-78. doi: 10.1111/bph.13172. Epub 2015 Jun 12.

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

Author information

1
Institute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Lübeck, Germany.
2
DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, Lübeck, Germany.
3
Department for Radiology and Nuclear Medicine, University of Lübeck, Lübeck, Germany.
4
Department of Pathology, University Clinic Schleswig-Holstein, Luebeck, Germany.
5
National Institute of Science and Technology in Nanobiopharmaceutics, Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
6
Max-Delbrück-Center for Molecular Medicine (MDC), Berlin, Germany.
7
DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany.
8
Center for Structural and Cell Biology in Medicine, Institute for Biology, University of Lübeck, Lübeck, Germany.
9
Charité - University Medicine Berlin, Berlin, Germany.

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 μg·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.

PMID:
25906670
PMCID:
PMC4523334
DOI:
10.1111/bph.13172
[Indexed for MEDLINE]
Free PMC Article

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