TRYPANOSOMA CRUZI MODULATION OF THE INNATE IMMUNE RESPONSE AND LIPID METABOLISM ON AN EXPERIMENTAL MODEL OF OBESITY

Buzios, RJ

Congreso; Congress of Sociedade Brasileira de Imunologia; 2014

Sociedade Brasileira de Imunologia

Introduction: About 11 million people in Latin America are infected with Trypanozoma cruzi protozoa (WHO, 2012). Adipose tissue is an important target of this infection contributing to dysregulation in fat and glucose metabolism. As obesity is a growing epidemic worldwide, our aim was to analyze the interplay of T.cruzi infection and obesity on innate immunity and lipid metabolism, in a diet-induced obesity model (DIO). Methods and Results: A DIO model of B6 male mice infected intraperitoneally (i.p) with 500 T. cruzi parasites (Tulahuen) was studied during 6 months: control (C), diet (D), diet-infection (DI) and infection (I) groups. Briefly, D and DI received 13% fat diet, 5% fructose in water and a single dose of streptozotocin (i.p, 8mg/Kg); while C and I received a normal chow diet. Increases in body weight and visceral adipose tissue (VAT) were significant in D group compared to C and DI. In DI, infection ameliorated both parameters and no significant difference was seen with group I. Blood triglycerides (Tg) and cholesterol (Ch), were determined by enzymatic methods. Dyslipidemia, given by a strong increase in Tg and Ch levels was found in D, while a significant decrease in both lipid levels was seen in DI. Lipoprotein electrophoretic analysis showed an increase in LDL and VLDL bands in D and DI, suggesting a pro-atherogenic profile. Parasites were seen in VAT by IFI; infiltrating cells were found in infected groups (H-E images) and adipocytes of minor size were observed in DI compared to D. IL-6, TNFα, leptin (pg/ml) and adiponectin (APN, ng/ml) were assayed by ELISA. Significant increases in lipolytic cytokines, IL-6 and TNFα, were found in DI group (2699±475; 135±6) compared to D (313±87; 51±2) and I (337±76; 89±9). A marked reduction in APN and leptin levels was seen in DI (6±1; 9887±1150) in relation to D (12±2; 188890±8000), accordingly to a decrease in body weight. As acute phase proteins (APP) are known to stimulate IL-6 and TNFα production, agarose electrophoresis was performed, showing an APP increase in DI. Analysis of CD36 in VAT by western blot showed an increased expression in D and DI, compared to C and I, respectively. MDA quantification by TBARS (µmol/µg ptna) revealed a strong lipid peroxidation in DI VAT (3.4±1) in comparison to D and I (0.8±0.1; 1±0.1). Conclusion: T. cruzi infection exacerbates inflammatory response seen in obese mice resulting in a lipolytic and a pro-atherogenic state. Supported by SIV-UCC and SECyT-UNC grants.