title: The brain renin-angiotensin system plays a crucial role in regulating body weight in diet-induced obesity in rats.
abstract: Reduced weight gain after treatment with AT1 receptor antagonists may involve a brain-related mechanism. Here, we investigated the role of the brain renin-angiotensin system on weight regulation and food behaviour, with or without additional treatment with telmisartan.
  
  
  
  Transgenic rats with a brain-specific deficiency in angiotensinogen (TGR(ASrAOGEN)) and the corresponding wild-type, Sprague Dawley (SD) rats were fed (3 months) with a high-calorie cafeteria diet (CD) or standard chow. SD and TGR(ASrAOGEN) rats on the CD diet were also treated with telmisartan (8 mg·kg(-1) ·d(-1) , 3 months).
  
  
  
  Compared with SD rats, TGR(ASrAOGEN) rats (i) had lower weights during chow feeding, (ii) did not become obese during CD feeding, (iii) had normal baseline leptin plasma concentrations independent of the feeding regimen, whereas plasma leptin of SD rats was increased due to CD, (iv) showed a reduced energy intake, (v) had a higher, strain-dependent energy expenditure, which is additionally enhanced during CD feeding, (vi) had enhanced mRNA levels of pro-opiomelanocortin and (vii) showed improved glucose control. Weight gain and energy intake in rats fed the CD diet were markedly reduced by telmisartan in SD rats but only to a minor extent in TGR(ASrAOGEN) rats.
  
  
  
  The brain renin-angiotensin system affects body weight regulation, feeding behaviour and metabolic disorders. When angiotensin II levels are low in brain, rats are protected from developing diet-induced obesity and obesity-related metabolic impairments. We further suggest that telmisartan at least partly lowers body weight via a CNS-driven mechanism.
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.|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: Ines
authors.initials: I
authors.lastname: Stölting
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, Campus Lübeck, Lübeck, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Thorns
authors.affiliation: 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.|CBBM (Center of Brain, Behavior and Metabolism), Lübeck, Germany.
authors.forename: Walter
authors.initials: W
authors.lastname: Raasch
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology; D001565:Benzoates / Q000008:administration & dosage / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004032:Diet / Q000009:adverse effects*; D008297:Male; D009765:Obesity / Q000209:etiology* / Q000378:metabolism*; D051381:Rats; D055647:Rats, Transgenic; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D000077333:Telmisartan
chemical_list: D001562:Benzimidazoles; D001565:Benzoates; D000077333:Telmisartan