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.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Schuchard J,Winkler M,Stölting I,Schuster F,Vogt FM,Barkhausen J,Thorns C,Santos RA,Bader M,Raasch Wdoi
10.1111/bph.13172subject
Has Abstractpub_date
2015-08-01 00:00:00pages
3764-78issue
15eissn
0007-1188issn
1476-5381journal_volume
172pub_type
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journal_title：British journal of pharmacology
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journal_title：British journal of pharmacology
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journal_title：British journal of pharmacology
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