title: Role of T regulatory lymphocytes in the pathogenesis of high-fructose diet-induced metabolic syndrome.
abstract: We recently showed that T regulatory lymphocytes (Treg), which are immune suppressors of inflammatory responses, play a role blunting the development of hypertension-induced injury. Treg are unchanged or decreased in children with metabolic syndrome, and therefore, their role in metabolic syndrome remains unclear. We hypothesized that Treg number or function would be depressed in a high-fructose diet-induced metabolic syndrome-like model in rats. Sprague-Dawley rats were fed normal chow or a high-fructose diet for 5 weeks. The high-fructose diet-induced a 3.8-fold increase in plasma triglycerides and a 14% reduction in high-density lipoprotein cholesterol (P<0.001). The high-fructose diet increased reactive oxygen species in aorta and periaortic adipose tissue 2.8-fold (P<0.05), and reduced nicotinamide adenine dinucleotide phosphate oxidase activity 1.9-fold in aorta, and 2.5-fold in the heart (P<0.05). It also increased plasma nitric oxide metabolite levels 6.4-fold (P<0.001). Western blots showed that the high-fructose diet increased ≥2.3-fold vascular and in platelet endothelial cell adhesion molecule 1 in aorta (P<0.01). It did not affect monocyte/macrophage aortic infiltration but caused a 2.4-fold increase in collagen deposition in the aortic media (P<0.01). No change in plasma interleukin-10 was detected. The percentage of spleen CD4+ CD25- and Treg (CD4+ CD25(high)) cells was unaltered by the high-fructose diet. However, cultured Treg from high-fructose diet-fed rats secreted 62% less interleukin-10 than control cells (P<0.05), suggesting a decreased Treg function, which could play a role in the development of cardiovascular complications of the metabolic syndrome.
authors.affiliation: Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, #B-127, 3755 Côte-Ste-Catherine Road, Montréal, Québec, Canada.
authors.forename: Avshalom
authors.initials: A
authors.lastname: Leibowitz
authors.forename: Asia
authors.initials: A
authors.lastname: Rehman
authors.forename: Pierre
authors.initials: P
authors.lastname: Paradis
authors.forename: Ernesto L
authors.initials: EL
authors.lastname: Schiffrin
mesh_terms: D000818:Animals; D015153:Blotting, Western; D019587:Dietary Supplements / Q000633:toxicity; D004195:Disease Models, Animal; D005632:Fructose / Q000633:toxicity; D007111:Immunity, Cellular / Q000502:physiology*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000209:etiology / Q000276:immunology*; D009569:Nitric Oxide / Q000097:blood; D018384:Oxidative Stress / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000097:blood; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D017382:Reactive Oxygen Species; D005632:Fructose; D009569:Nitric Oxide
keywords: inflammation; interleukin-10; oxidative stress; vascular remodeling