RESUMO
Brown adipose tissue (BAT) and white adipose tissue (WAT) and adipocytes are targets of Trypanosoma cruzi infection. Adipose tissue obtained from CD-1 mice 15 days after infection, an early stage of infection revealed a high parasite load. There was a significant increase in macrophages in infected adipose tissue and a reduction in lipid accumulation, adipocyte size, and fat mass and increased expression of lipolytic enzymes. Infection increased levels of Toll-like receptor (TLR) 4 and TLR9 and in the expression of components of the mitogen-activated protein kinase pathway. Protein and messenger RNA (mRNA) levels of peroxisome proliferator-activated receptor γ were increased in WAT, whereas protein and mRNA levels of adiponectin were significantly reduced in BAT and WAT. The mRNA levels of cytokines, chemokines, and their receptors were increased. Nuclear Factor Kappa B levels were increased in BAT, whereas Iκκ-γ levels increased in WAT. Adipose tissue is an early target of T. cruzi infection.
Assuntos
Adipócitos/metabolismo , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Doença de Chagas/parasitologia , RNA Mensageiro/metabolismo , Transdução de Sinais , Trypanosoma cruzi , Adipócitos/parasitologia , Adipócitos/patologia , Adiponectina/metabolismo , Tecido Adiposo Marrom/parasitologia , Tecido Adiposo Marrom/patologia , Tecido Adiposo Branco/parasitologia , Tecido Adiposo Branco/patologia , Animais , Doença de Chagas/patologia , Quimiocinas/metabolismo , Citocinas , Quinase I-kappa B/metabolismo , Masculino , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , PPAR gama/metabolismo , Receptores de Quimiocinas/metabolismo , Receptor 4 Toll-Like/metabolismo , Receptor Toll-Like 9/metabolismoRESUMO
Mice carrying a defective leptin receptor gene (db/db mice) are metabolically challenged and upon infection with Trypanosoma cruzi (Brazil strain) suffer high mortality. In genetically modified db/db mice, (NSE-Rb db/db mice), central leptin signaling is reconstituted only in the brain, which is sufficient to correct the metabolic defects. NSE-Rb db/db mice were infected with T. cruzi to determine the impact of the lack of leptin signaling on infection in the absence of metabolic dysregulation. Parasitemia levels, mortality rates, and tissue parasitism were statistically significantly increased in infected db/db mice compared with those in infected NSE-Rb db/db and FVB wild-type mice. There was a reduction in fat mass and blood glucose level in infected db/db mice. Plasma levels of several cytokines and chemokines were statistically significantly increased in infected db/db mice compared with those in infected FVB and NSE-Rb db/db mice. These findings suggest that leptin resistance in individuals with obesity and diabetes mellitus may have adverse consequences in T. cruzi infection.