Chagas disease in an obesogenic context: a highlight role for adipose visceral tissue as a chronic reservoir of Trypanosoma cruzi that contributes to associated cardiovascular complications

CABALÉN MARÌA E; SANMARCO LM; EBERHART N; CABRAL MARÍA F; PONCE N; ANDRADA MC; GEA S; AOKI MP; CANO R

Congreso; Reunion Conjunta de Sociedades de Biociencias; 2017

Chagas disease and obesity are chronic and public health concerns with associated cardiovascular complications (CV). Oxidative stress (OS) and inflammation are common mechanisms that pre dispose to CV. We hypothesize that in an obesogenic context, the immune-metabolic dysregulation exerted by T. cruzi infection could drive CV.To elucidate this complex interrelation, we evaluate the lipid and lipoprotein systemic changes and the oxidative and immune-in flammatory alterations in visceral adipose tissue (VAT) in uninfected C57BL/6 mice feed with LFD (4% fat diet) or DIO (14% fat/ 5% fructose diet), or infected (LFD+I and DIO+I) groups. Although an improvement on plasma triglycerides (TG) and total cholesterol (TC) levels were seen in DIO+I compared to DIO mice (p<0.001; p<0.001), apoB100 levels were increased in all groups in relation to LFD (p< 0.05); suggesting the presence of atherogenic small and dense LDL particles in infected groups. Concomitant qualitative differences in lipoprotein bands were observed. Signifcant decreasesin the adiponectin levels were seen in both infected groups compared to DIO and LFD (p<0.001; p<0.001). In VAT, inflammatory cell-infltration (p<0.001) and OS (measured by lipid peroxidation) were exacerbated in DIO+I compared to LFD+I mice (p<0.05). Despite a higher number of macrophages observed in VAT (ATM) from DIO+I than in LFD+I mice (p<0.001), they presented a M2 pheno type (F4/80+CD11c-CD206+). Furthermore, increased CD36 expression (p<0.05) and parasite load (p<0.05) was seen in VAT from DIO+I compared to LFD+I. Conversely in heart, a low parasite loadwas observed independent of the diet, highlighting VAT as a more suitable chronic reservoir. The strong inflammatory and oxidative response in an obesogen ic context is probably counter-balanced by the parasite, which mayinduce the polarization of ATM to a M2 phenotype to favor its own survival. Thus, parasite persistence would be a key trigger in the progression of CV Chagas disease.