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

• Published in: Hormone and metabolic research Vol. 47; no. 4; p. 253
• Main Authors: Ojima, A, Matsui, T, Nakamura, N, Higashimoto, Y, Ueda, S, Fukami, K, Okuda, S, Yamagishi, S
• Format: Journal Article
• Language: English
• Published: Germany 01.04.2015
• Subjects: Adipocytes - drug effects; Adipocytes - pathology; Adiponectin - genetics; Animals; Aptamers, Nucleotide - administration & dosage; Blood Glucose - analysis; Cell Size - drug effects; Diet; Fructose - administration & dosage; Gene Expression - drug effects; Glycation End Products, Advanced - antagonists & inhibitors; Glycation End Products, Advanced - genetics; Insulin Resistance; Male; Oxidative Stress - drug effects; Rats; Rats, Wistar; Real-Time Polymerase Chain Reaction; Receptor for Advanced Glycation End Products - antagonists & inhibitors; Weight Gain - drug effects
• ISSN: 1439-4286
• DOI: 10.1055/s-0034-1385904

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.