EFFECT OF TRYPANOSOMA CRUZI INFECTION AND NUTRITION ON THE MODULATION OF METABOLIC PARAMETERS AND IMMUNE INNATE EXPRESSION OF TOLL-LIKE RECEPTORS, CYTOKINES AND ADIPOKINES IN AN EXPERIMENTAL NON-GENETIC OBESITY MODEL

CABALÉN M.E; CABRAL MF; ANDRADA MC; GEA S; CANO RC

NATAL

Congreso; 11th International Congress on Inflammation; 2013

Sociedade Brasileira do Immunologia

Introduction: Obesity is a growing epidemic worldwide, and by 2015 about 700 million adults will be obese. Microbes are linked to obesity, but conclusive evidence for a key role of parasites is lacking. About 11 million people are infected with T. cruzi, which causes Chagas disease, endemic to Latin America (WHO, 2012). Our aim was to investigate the impact of this infection and nutrition, in metabolic and innate immune response, in a diet-induced obesity model (Medicina; 72:237, 2012). Methods and Results: Three C57BL/6 male groups were studied up to 6 months (m): control (C, normal chow diet), diet (D) and diet-infection (DI). D and DI received 13% fat diet, 5% fructose in water and an intraperitoneal (i.p) dose of streptozotocin. DI was infected i.p with 500 Tulahuen strain parasites. Triglycerides, cholesterol, glucose (Tg, Ch, G; mg/dl) and ALT (U/L) (Enzymatic methods) levels were determined. HOMA-IR was used to evaluate insulin-resistance (IR). Lipoproteins (LP) and acute phase (AP) proteins were analyzed by electrophoresis. Adiponectin (ng/ml) and cytokines (pg/ml) were measured by ELISA. Tissue samples were obtained for H-E and TLR2/4 immunofluorescence studies. Western Blot: TLR2/4 were analyzed in visceral adipose tissue (VAT) lysates. Nutrition impact was higher in D than in DI and C mice. Up to 6m, a significant increase in body weight, waist diameter and body mass index was found in D. A 2 and 4-fold increment in %VAT in D vs DI and C was shown. In D, hyperglycemia and IR were found at 1-3m. Dyslipidemia was encountered in D and DI with increases in Tg and Ch levels and changes in the LP pattern (high VLDL and LDL; low HDL). An early AP reaction was seen in DI (α1; α2 augments) as in D. IL-6 and TNF-α were also increased; as expected, higher levels were found in DI (2699±475; 135±6) than in D mice (313±87; 51±2). Adiponectin was synergistically reduced in DI (4±0.5; 5±1; 6±1) vs D (8±0.5; 9±1; 12±2) at 1-3-6m. In D VAT, cell hypertrophy, marked immune cell infiltration and TLR2/4 over-expression were seen at 6m. Infection induced a minor cell size and down-regulation of TLR4, but higher infiltration and TLR2 expression vs D. Hepatic steatosis was found in D, with a 3-fold increase in TG content vs DI. However, an intense local infiltration and increased ALT activity was seen in DI. Conclusion: In our model, T. cruzi infection improves the metabolic state but induces a stronger inflammatory response. Supported by SIV-UCC and SECyT-UNC grants.