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.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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) ).
  
  
  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
  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.
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Lübeck, Germany.|DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, Lübeck, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Schuchard
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Lübeck, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Winkler
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Lübeck, Germany.
authors.forename: Ines
authors.initials: I
authors.lastname: Stölting
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Lübeck, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Schuster
authors.affiliation: Department for Radiology and Nuclear Medicine, University of Lübeck, Lübeck, Germany.
authors.forename: Florian M
authors.initials: FM
authors.lastname: Vogt
authors.affiliation: Department for Radiology and Nuclear Medicine, University of Lübeck, Lübeck, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Barkhausen
authors.affiliation: Department of Pathology, University Clinic Schleswig-Holstein, Luebeck, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Thorns
authors.affiliation: 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.
authors.forename: Robson A
authors.initials: RA
authors.lastname: Santos
authors.affiliation: 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.|Max-Delbrück-Center for Molecular Medicine (MDC), Berlin, Germany.|DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany.|Center for Structural and Cell Biology in Medicine, Institute for Biology, University of Lübeck, Lübeck, Germany.|Charité - University Medicine Berlin, Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Bader
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Lübeck, Germany.|DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, Lübeck, Germany.
authors.forename: Walter
authors.initials: W
authors.lastname: Raasch
mesh_terms: D000803:Angiotensin I / Q000378:metabolism*; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D030801:Animals, Genetically Modified; D001562:Benzimidazoles / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001565:Benzoates / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004032:Diet / Q000009:adverse effects*; D002149:Energy Intake / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D007333:Insulin Resistance / Q000235:genetics; D020738:Leptin / Q000494:pharmacology; D008297:Male; D009765:Obesity / Q000188:drug therapy* / Q000209:etiology*; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000819:agonists* / Q000378:metabolism; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000077333:Telmisartan; D015430:Weight Gain / Q000187:drug effects*; D015431:Weight Loss / Q000187:drug effects
chemical_list: C092006:7-Ala-angiotensin (1-7); D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D020738:Leptin; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D000804:Angiotensin II; D000803:Angiotensin I; C118790:angiotensin I (1-7); D000077333:Telmisartan