title: 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.affiliation: Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Ojima
authors.affiliation: Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Matsui
authors.affiliation: Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Nakamura
authors.affiliation: Department of Chemistry, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Higashimoto
authors.affiliation: Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Ueda
authors.affiliation: Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Fukami
authors.affiliation: Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Okuda
authors.affiliation: Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Yamagishi
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000473:pathology*; D052242:Adiponectin / Q000235:genetics; D000818:Animals; D052157:Aptamers, Nucleotide / Q000008:administration & dosage*; D001786:Blood Glucose / Q000032:analysis*; D048429:Cell Size / Q000187:drug effects; D004032:Diet; D005632:Fructose / Q000008:administration & dosage*; D015870:Gene Expression / Q000187:drug effects; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors* / Q000235:genetics; D007333:Insulin Resistance; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D000067759:Receptor for Advanced Glycation End Products / Q000037:antagonists & inhibitors*; D015430:Weight Gain / Q000187:drug effects
chemical_list: D052242:Adiponectin; D052157:Aptamers, Nucleotide; D001786:Blood Glucose; D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D005632:Fructose