DNA Aptamer Raised Against Advanced Glycation End Products (AGEs) Improves Glycemic Control and Decreases Adipocyte Size in Fructose-Fed Rats by Suppressing AGE-RAGE Axis

A. Ojima; T. Matsui; N. Nakamura; Y. Higashimoto; S. Ueda; K. Fukami; S. Okuda; S. Yamagishi

doi:10.1055/s-0034-1385904

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2015; 47(04): 253-258
DOI: 10.1055/s-0034-1385904

Endocrine Research

DNA Aptamer Raised Against Advanced Glycation End Products (AGEs) Improves Glycemic Control and Decreases Adipocyte Size in Fructose-Fed Rats by Suppressing AGE-RAGE Axis

Authors

A. Ojima

¹Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan
T. Matsui

¹Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan
N. Nakamura

¹Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan
Y. Higashimoto

²Department of Chemistry, Kurume University School of Medicine, Kurume, Japan
S. Ueda

³Department of Medicine, Kurume University School of Medicine, Kurume, Japan
K. Fukami

³Department of Medicine, Kurume University School of Medicine, Kurume, Japan
S. Okuda

³Department of Medicine, Kurume University School of Medicine, Kurume, Japan
S. Yamagishi

¹Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan

Abstract

Advanced glycation end products (AGEs) decrease adiponectin expression and suppress insulin signaling in cultured adipocytes through the interaction with a receptor for AGEs (RAGE) via oxidative stress generation. We have recently found that high-affinity DNA aptamer directed against AGE (AGE-aptamer) prevents the progression of experimental diabetic nephropathy by blocking the harmful actions of AGEs in the kidney. This study examined the effects of AGE-aptamer on adipocyte remodeling, AGE-RAGE-oxidative stress axis, and adiponectin expression in fructose-fed rats. Although AGE-aptamer treatment by an osmotic mini pump for 8 weeks did not affect serum insulin levels, it significantly decreased average fasting blood glucose and had a tendency to inhibit body weight gain in fructose-fed rats. Furthermore, AGE-aptamer significantly suppressed the increase in adipocyte size and prevented the elevation in AGEs, RAGE, and an oxidative stress marker, 8-hydroxydeoxyguanosine (8-OHdG), levels in adipose tissues of fructose-fed rats at 14-week-old, while it restored the decrease in adiponectin mRNA levels. Our present study suggests that AGE-aptamer could improve glycemic control and prevent adipocyte remodeling in fructose-fed rats partly by suppressing the AGE-RAGE-mediated oxidative stress generation. AGE-aptamer might be a novel therapeutic strategy for fructose-induced metabolic derangements.

Key words

AGEs - RAGE - oxidative stress - adiponectin - adipocytes - aptamer

Full Text

References

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