Introduction e metabolic syndrome is characterized by the association of insulin resistance (IR) with alterations in glucose tolerance or type 2 diabetes, central obes- ity, hypertension and dyslipidemia. is condition has an increasing incidence in human populations consuming high calorie diets and with a tendency to a sedentary behaviour (Reaven, 1988; Guthrie et al., 2000). All the abnormalities involved in IR constitute a high risk for developing cardiovascular disease, the main cause of morbidity and mortality in developed and developing countries. Feeding rats with high sucrose (SRD) or fructose (FRD) induces early changes in glucose and lipid metabolism that resemble the profile of the human metabolic syndrome, thus providing a useful model to study its consequences as well as to design different preventive strategies (Tobey et al., 1982; Gutman et al., 1987; ornburn et al., 1989; Dai et al., 1994; Catena et al., 2003). is experimental model is particularly appropriate to study the development of IR and is Archives of Physiology and Biochemistry, 2010; 116(1): 42-49 ORIGINAL ARTICLE Glycoxidative stress-induced damage on lipid profile in a fructose-enriched diet model of insulin resistance in rats M.E. García 1 , C.A. Marra 2 , and O.R. Rebolledo 1 1 CENEXA (Centro de Endocrinología Experimental y Aplicada, UNLP-CONICET La Plata, PAHO/WHO Collaborating Center), and 2 INIBIOLP (Instituto de Investigaciones Bioquímicas de La Plata, UNLP-CONICET La Plata, Cátedra de Bioquímica y Biología Molecular), Facultad de Ciencias Médicas, Universidad Nacional de La Plata, 60 y 120 (1900) La Plata, Argentina Abstract Objective: To study alterations in plasma lipid profile and oxidative damage to lipoprotein fractions (LF) and their fatty acids during an early insulin-resistant and increased oxidative state developed by a fructose-rich diet (FRD). Methods and results: Wistar rats were fed a commercial diet with (FRD) or without (CD) 10% fructose in the drinking water. After 3 weeks, plasma glucose, triglyceride (TG), insulin (I), fructosamine (F), free fatty acids (FFA) and lipid profile (total cholesterol [TC] and HDL-C, LDL-C and VLDL-C sub-fractions) were determined. The insulin sensitivity HOMA index was assessed. FRD-fed rats had higher plasma TG, I, and F levels; increased HOMA; decreased HDL-C and LDL-C; augmented VLDL-C and TC/HDL-C, and TG/HDL-C atherogenic risk scores. LF of FRD rats had increased oxidative damage on the fatty acyl profile and in copper-induced lipoperoxidation. Conclusions: Fructose feeding early increases the atherogenic risk inducing an insulin resistant-glycoxidative state that affects plasma lipid profiles. Keywords: Oxidative stress; lipid peroxidation; lipoproteins; fructose diet; dyslipidemia Non-conventional abbreviations: CETP, cholesteryl-ester-tansfer protein; c-GLC, capillary gas-liquid chromatography; CD, control diet; FAMEs, fatty acid methyl esters; FFA, free fatty acids; FRD, fructose-rich diet; LCAT, lecitine-cholesterol-acyltransferase; LPL, lipoprotein-lipase; PUFA, polyunsaturated fatty acids; ROS, reactive oxygen species; TBARS, thiobarbituric acid reactive substances Address for Correspondence: Prof. Dr. Oscar Rebolledo, CENEXA (Centro de Endocrinología Experimental y Aplicada) UNLP-CONICET LA PLATA, PAHO/WHO Collaborating Center). Tel: +54 221 423 6712. Fax: +54 221 422 2081. E-mail: oscar_rebolledo@yahoo.com.ar (Received 14 October 2009; revised 30 November 2009; accepted 03 December 2009) ISSN 1381-3455 print/ISSN 1744-4160 online © 2010 Informa UK Ltd DOI: 10.3109/13813450903527713 http://www.informahealthcare.com/arp Archives of Physiology and Biochemistry Downloaded from informahealthcare.com by University of California San Diego on 03/18/11 For personal use only.