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.

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.

• Authors: A Ojima, T Matsui, N Nakamura, Y Higashimoto, S Ueda, K Fukami, S Okuda, S Yamagishi
• Journal: Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme (Horm Metab Res) Vol. 47 Issue 4 Pg. 253-8 (Apr 2015) ISSN: 1439-4286 [Electronic] Germany
• PMID: 25105541 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © Georg Thieme Verlag KG Stuttgart · New York.

Chemical References

• Adiponectin
• Aptamers, Nucleotide
• Blood Glucose
• Glycation End Products, Advanced
• Receptor for Advanced Glycation End Products
• Fructose

Topics

• Adipocytes (drug effects, 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, 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)