title: Preventing leptin resistance by blocking angiotensin II AT1 receptors in diet-induced obese rats.
abstract: OBJECTIVE
  AT1 receptor blockers (ARBs) represent an approach for treating metabolic syndrome due to their potency in reducing hypertension, body weight and onset of type 2 diabetes. The mechanism underlying ARB-induced weight loss is still unclear.
  
  
  METHODS
  Leptin resistance tests (LRTs) in diet-induced obese or lean rats were conducted to determine whether telmisartan (8 mg·kg(-1) ·day(-1) , 14 days) enhances leptin sensitivity. Phosphorylation of signal transducer and activator of transcription 3 (pSTAT3) staining was performed in hypothalami to determine leptin transport across the blood-brain barrier.
  
  
  RESULTS
  Telmisartin reduced weight gain, food intake and plasma leptin but blood pressure remained unchanged. The 24 h profiles of plasma leptin after saline injections were similar in controls and telmisartan-treated rats, but after leptin injections were higher in controls and slightly lower in telmisartan-treated animals. After telmisartan, energy intake during LRT was lower in leptin- than in saline-pretreated rats, but remained unchanged in controls, irrespectively of whether rats received saline or leptin. Leptin minimized the gain in body weight during LRT in telmisartan-treated rats as compared with saline-treated animals. pSTAT3 staining was reduced in cafeteria diet-fed rats as compared with chow-fed rats but this was normalized by telmisartan. Telmisartin reduced hypothalamic mRNA levels of the orexigenic peptides melanin-concentrating hormone and prepro-orexin.
  
  
  CONCLUSIONS
  Rats fed a cafeteria diet develop leptin resistance after 2 weeks. Leptin sensitivity was preserved by telmisartan treatment even in rats fed a cafeteria diet. This pleiotropic effect is not related to the hypotensive action of telmisartan.
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: Helge
authors.initials: H
authors.lastname: Müller-Fielitz
authors.forename: Margot
authors.initials: M
authors.lastname: Lau
authors.forename: Cathleen
authors.initials: C
authors.lastname: Geißler
authors.forename: Lars
authors.initials: L
authors.lastname: Werner
authors.forename: Martina
authors.initials: M
authors.lastname: Winkler
authors.forename: Walter
authors.initials: W
authors.lastname: Raasch
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D004032:Diet / Q000009:adverse effects*; D020738:Leptin / Q000097:blood / Q000378:metabolism*; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D020738:Leptin; D044140:Receptor, Angiotensin, Type 1