title: AT2 receptor deficiency attenuates adipocyte differentiation and decreases adipocyte number in atherosclerotic mice.
abstract: BACKGROUND
  Previous reports indicated that blockade of AT(1) receptor stimulation attenuated adipocyte dysfunction. However, the effects of AT(2) receptor stimulation on adipose tissue were not yet clear. In the present study, we examined the adipose tissue dysfunction in atherosclerotic apolipoprotein E knockout (ApoEKO) mice with AT(2) receptor deficiency.
  
  
  METHODS
  Male ApoEKO and AT(2) receptor/ApoE knockout (AT(2)/ApoEKO) mice at 6 weeks of age were treated with a normal diet or a high-cholesterol diet (HCD: 1.25% cholesterol). Markers for adipocyte differentiation and inflammation in adipose tissue were assayed with real-time reverse-transcription-PCR and western blot.
  
  
  RESULTS
  Compared with ApoEKO mice, AT(2)/ApoEKO mice with a normal diet showed only a decrease in expression of adiponectin and CCAAT/enhancer binding protein delta (C/EBPdelta) in epididymal adipose tissue without changes in body weight, adipose tissue weight, and adipocyte number even at 6 months of age. After HCD for 4 weeks, the weight of both epididymal and retroperitoneal adipose tissue in AT(2)/ApoEKO mice was greater than that in ApoEKO mice without a change in body weight. Plasma concentrations of cholesterol and fatty acids were higher in AT(2)/ApoEKO mice than in ApoEKO mice. In adipose tissue of AT(2)/ApoEKO mice, the adipocyte number was decreased and the expression of peroxisome proliferator-activated receptor gamma (PPARgamma), C/EBPalpha, and aP2 was lower than that in ApoEKO mice, in association with an increase in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity.
  
  
  CONCLUSIONS
  These results suggest that AT(2) receptor stimulation in adipose tissue is involved in the improvement of adipocyte differentiation and adipose tissue dysfunction in atherosclerotic model.
authors.affiliation: Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Shitsukawa, Ehime, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Iwai
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Tomono
authors.forename: Shinji
authors.initials: S
authors.lastname: Inaba
authors.forename: Harumi
authors.initials: H
authors.lastname: Kanno
authors.forename: Izumi
authors.initials: I
authors.lastname: Senba
authors.forename: Masaki
authors.initials: M
authors.lastname: Mogi
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Horiuchi
mesh_terms: D017667:Adipocytes / Q000502:physiology*; D000273:Adipose Tissue / Q000187:drug effects / Q000473:pathology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D057912:Angiotensin II Type 2 Receptor Blockers; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000473:pathology* / Q000503:physiopathology; D002452:Cell Count; D002454:Cell Differentiation / Q000502:physiology; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000172:deficiency* / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D000068756:Valsartan
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D001057:Apolipoproteins E; D002791:Cholesterol, Dietary; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; D000068756:Valsartan; D019255:NADPH Oxidases; D014633:Valine