Chronic Trypanosoma cruzi infection potentiates adipose tissue macrophage polarization toward an anti-inflammatory M2 phenotype and contributes to diabetes progression in a diet-induced obesity model.

Chronic obesity and Chagas disease (caused by the protozoan Trypanosoma cruzi) represent serious public health concerns. The interrelation between parasite infection, adipose tissue, immune system and metabolism in an obesogenic context, has not been entirely explored. A novel diet-induced obesity model (DIO) was developed in C57BL/6 wild type mice to examine the effect of chronic infection (DIO+I) on metabolic parameters and on obesity-related disorders. Dyslipidemia, hyperleptinemia, and cardiac/hepatic steatosis were strongly developed in DIO mice. Strikingly, although these metabolic alterations were collectively improved by infection, plasmatic apoB100 levels remain significantly increased in DIO+I, suggesting the presence of pro-atherogenic small and dense LDL particles. Moreover, acute insulin resistance followed by chronic hyperglycemia with hypoinsulinemia was found, evidencing an infection-related-diabetes progression. These lipid and glucose metabolic changes seemed to be highly dependent on TLR4 expression since TLR4-/- mice were protected from obesity and its complications. Notably, chronic infection promoted a strong increase in MCP-1 producing macrophages with a M2 (F4/80+CD11c-CD206+) phenotype associated to oxidative stress in visceral adipose tissue of DIO+I mice. Importantly, infection reduced lipid content but intensified inflammatory infiltrates in target tissues. Thus, parasite persistence in an obesogenic environment and the resulting host immunometabolic dysregulation may contribute to diabetes/atherosclerosis progression.

Trypanosoma cruzi infection is a potent risk factor for non-alcoholic steatohepatitis enhancing local and systemic inflammation associated with strong oxidative stress and metabolic disorders.

BACKGROUND: The immune mechanisms underlying experimental non-alcoholic steatohepatitis (NASH), and more interestingly, the effect of T. cruzi chronic infection on the pathogenesis of this metabolic disorder are not completely understood. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated immunological parameters in male C57BL/6 wild type and TLR4 deficient mice fed with a standard, low fat diet, LFD (3% fat) as control group, or a medium fat diet, MFD (14% fat) in order to induce NASH, or mice infected intraperitoneally with 100 blood-derived trypomastigotes of Tulahuen strain and also fed with LFD (I+LFD) or MFD (I+MFD) for 24 weeks. We demonstrated that MFD by itself was able to induce NASH in WT mice and that parasitic infection induced marked metabolic changes with reduction of body weight and steatosis revealed by histological studies. The I+MFD group also improved insulin resistance, demonstrated by homeostasis model assessment of insulin resistance (HOMA-IR) analysis; although parasitic infection increased the triglycerides and cholesterol plasma levels. In addition, hepatic M1 inflammatory macrophages and cytotoxic T cells showed intracellular inflammatory cytokines which were associated with high levels of IL6, IFNγ and IL17 plasmatic cytokines and CCL2 chemokine. These findings correlated with an increase in hepatic parasite load in I+MFD group demonstrated by qPCR assays. The recruitment of hepatic B lymphocytes, NK and dendritic cells was enhanced by MFD, and it was intensified by parasitic infection. These results were TLR4 signaling dependent. Flow cytometry and confocal microscopy analysis demonstrated that the reactive oxygen species and peroxinitrites produced by liver inflammatory leukocytes of MFD group were also exacerbated by parasitic infection in our NASH model. CONCLUSIONS: We highlight that a medium fat diet by itself is able to induce steatohepatitis. Our results also suggest a synergic effect between damage associated with molecular patterns generated during NASH and parasitic infection, revealing an intense cross-talk between metabolically active tissues, such as the liver, and the immune system. Thus, T. cruzi infection must be considered as an additional risk factor since exacerbates the inflammation and accelerates the development of hepatic injury.

Identification of volatile compounds of Clinopodium odorum (Lamiaceae):A comparison between HS-SPME and classic hydrodistillation / Identificación de compuestos volátiles de Clinopodium odorum (Lamiaceae): Una comparación entre HS-SPME ehidrodestilación clásica

In the present work an analytical methodology to micro scale based on the use of the HS-SPME/GC-MS to determine volatile compounds present in Clinopodium odorum (Griseb.) Harley (Lamiaceae)was optimized and settled differences and similarities with itsessential oil. A systematic description of the volatile components of flowers, stems, leaves and combined aerial parts (whole plant) was constructed via GC-MS analyses of HS-SPME adsorbed compounds and of essential oils obtained through hydrodistillation of the same tissues. Pulegone was the main component of both the HS-SPME analysis and essential oil analysis. In addition, piperitenone oxide andpiperitone oxide were the other main components in the essential oil whereas in the HS-SPME analysis cis-isopulegone and menthone prevailed. The HS-SPME method can achieve comparable results to those obtained by essential oil analysis, by using very fewer samples, ashorter extraction time and a much simpler procedure.

En el presente trabajo se ha optimizado una metodología analítica a micro-escala basada en HS-SPME/GC-MS para determinar los compuestos volátiles presentes en Clinopodium odorum (Griseb.) Harley (Lamiaceae), y se establecieron diferencias y similitudes con su aceite esencial. Se realizó una descripción sistemática de los componentes volátiles de flores, tallos, hojas y partes aéreas combinadas(planta entera) a partir de los análisis por GC-MS a través del sistema HS-SPME y de los aceites esenciales. Pulegona fue el componenteprincipal tanto del análisis por HS-SPME, como del aceite esencial. Además, el óxido de piperitenona y el óxido de piperitona eran los otroscomponentes principales en el aceite esencial mientras que en el análisis por HS-SPME, prevalecieron cis-isopulegona y mentona. El método de HS-SPME puede lograr resultados comparables a los obtenidos por el análisis de aceite esencial, mediante el uso de muestras de menor tamaño, un tiempo de extracción más corto y un procedimiento más simple.