Receptor for advanced glycation end-products (RAGE) regulation of adiposity and adiponectin is associated with atherogenesis in apoE-deficient mouse.
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.
Ueno
Hiroki
H
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.
Koyama
Hidenori
H
Shoji
Takuhito
T
Monden
Masayo
M
Fukumoto
Shinya
S
Tanaka
Shinji
S
Otsuka
Yoshiko
Y
Mima
Yohei
Y
Morioka
Tomoaki
T
Mori
Katsuhito
K
Shioi
Atsushi
A
Yamamoto
Hiroshi
H
Inaba
Masaaki
M
Nishizawa
Yoshiki
Y
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
D052242:Adiponectin; D001057:Apolipoproteins E; D017127:Glycation End Products, Advanced; D014409:Tumor Necrosis Factor-alpha