title: Receptor for advanced glycation end-products (RAGE) regulation of adiposity and adiponectin is associated with atherogenesis in apoE-deficient mouse.
abstract: OBJECTIVE
  Receptor for advanced glycation end-products (RAGE) has been shown to be involved in cardiovascular diseases. We examined the involvement of RAGE in atherosclerosis under non-diabetic status, and its relation to the effect on adiposity.
  
  
  METHODS
  Apolipoprotein E (apoE)(-/-)RAGE(+/+) or apoE(-/-)RAGE(-/-) mice were fed with an atherogenic diet or the standard chow diet. Adiposity was determined by weight of epididymal adipose tissue, adipocyte size and serum adiponectin. Aortic atherosclerosis was morphometrically determined.
  
  
  RESULTS
  ApoE(-/-)RAGE(-/-) mice exhibited significantly less total aortic plaque area than apoE(-/-)RAGE(+/+) mice. Body weight, epididymal fat weight, and epididymal adipocyte size were also significantly less in apoE(-/-)RAGE(-/-) mice than apoE(-/-)RAGE(+/+) mice. Serum adiponectin, but not tumor necrosis factor-alpha, was significantly higher in apoE(-/-)RAGE(-/-) mice than apoE(-/-)RAGE(+/+) mice. Simple regression analysis revealed that the total aortic plaque area was positively associated with epididymal fat weight, epididymal adipocyte size, and negatively with serum adiponectin levels. Multiple regression analyses revealed that RAGE genotype and serum adiponectin were mutually interrelated in determining aortic atherosclerosis. Finally, immunohistochemical and real-time RT-PCR analyses revealed that RAGE was indeed expressed in both adipocytes and endothelial cells in epididymal adipose tissue.
  
  
  CONCLUSIONS
  RAGE-mediated regulation of adiposity in non-diabetic status could be attributable to the progression of atherosclerosis.
authors.affiliation: Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ueno
authors.forename: Hidenori
authors.initials: H
authors.lastname: Koyama
authors.forename: Takuhito
authors.initials: T
authors.lastname: Shoji
authors.forename: Masayo
authors.initials: M
authors.lastname: Monden
authors.forename: Shinya
authors.initials: S
authors.lastname: Fukumoto
authors.forename: Shinji
authors.initials: S
authors.lastname: Tanaka
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Otsuka
authors.forename: Yohei
authors.initials: Y
authors.lastname: Mima
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Morioka
authors.forename: Katsuhito
authors.initials: K
authors.lastname: Mori
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shioi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Masaaki
authors.initials: M
authors.lastname: Inaba
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Nishizawa
mesh_terms: D052242:Adiponectin / Q000097:blood* / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D000821:Animal Feed; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis; D004036:Diet, Atherogenic; D005786:Gene Expression Regulation; D017127:Glycation End Products, Advanced / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D052242:Adiponectin; D001057:Apolipoproteins E; D017127:Glycation End Products, Advanced; D014409:Tumor Necrosis Factor-alpha