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Erschienen in: Zeitschrift für Gerontologie und Geriatrie 2/2012

01.02.2012 | Beiträge zum Themenschwerpunkt

RAGE influences obesity in mice

Effects of the presence of RAGE on weight gain, AGE accumulation, and insulin levels in mice on a high fat diet

verfasst von: B. Leuner, M. Max, K. Thamm, C. Kausler, Y. Yakobus, A. Bierhaus, S. Sel, B. Hofmann, R.-E. Silber, A. Simm, Dr. N. Nass

Erschienen in: Zeitschrift für Gerontologie und Geriatrie | Ausgabe 2/2012

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Abstract

Background

The metabolic syndrome is defined by the presence of obesity, insulin resistance, dyslipidemia, and hypertension. Advanced glycation end products (AGEs) are stable end products of the Maillard reaction, whereby AGE accumulation is considered not only a biomarker of aging but is also associated with several degenerative diseases. AGEs are recognized by several receptor molecules of which the receptor of AGEs (RAGE) is currently the most intensively studied receptor. Activation of RAGE causes an unfavorable proinflammatory state and deletion of RAGE in diabetic animals has been reported to protect against atherosclerosis. AGEs and a high fat diet are associated with cardiovascular diseases, whereas is still not clear whether a direct link between high fat nutrition and AGEs exists in vivo.

Materials and methods

C57BL/6 and C57BL/6 RAGE −/− mice were fed a high fat diet to induce obesity. Weight, insulin, lipid levels, AGE modifications, and cardiac gene expression were analyzed.

Results

The absence of RAGE resulted in accelerated weight gain, increased plasma cholesterol, and higher insulin levels in obese mice. The hearts of normal and obese RAGE −/− mice contained lower levels of the AGE arginine–pyrimidine and 3DG-imidazolone than RAGE + / + animals. RAGE −/− mice also exhibited lower expression of the genes encoding the antioxidative enzymes MnSOD, Cu/ZnSOD, and ceruloplasmin in cardiac tissue, whereas the AGE receptors AGER-1, -2, and -3 were equally expressed in both genotypes. Obese mice of both strains expressed increased amounts of AGER-2. Only obese RAGE + / + mice exhibited a reduced mRNA accumulation of Cu/Zn SOD.

Conclusion

These data suggest that RAGE is involved in the development of obesity and insulin resistance.
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Metadaten
Titel
RAGE influences obesity in mice
Effects of the presence of RAGE on weight gain, AGE accumulation, and insulin levels in mice on a high fat diet
verfasst von
B. Leuner
M. Max
K. Thamm
C. Kausler
Y. Yakobus
A. Bierhaus
S. Sel
B. Hofmann
R.-E. Silber
A. Simm
Dr. N. Nass
Publikationsdatum
01.02.2012
Verlag
Springer-Verlag
Erschienen in
Zeitschrift für Gerontologie und Geriatrie / Ausgabe 2/2012
Print ISSN: 0948-6704
Elektronische ISSN: 1435-1269
DOI
https://doi.org/10.1007/s00391-011-0279-x

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