Estudo das alterações metabólicas e inflamatórias que acompanham a inflamação intestinal experimental

Abstract

Inflammatory bowel diseases (IBD) are chronic diseases whose incidence is increasing worldwide. Prebiotics and probiotics are promising therapeutics strategies in the treatment of IBD due to the ability to modulate the intestinal microbiota, which is one potential factor that triggers these diseases in susceptible individuals. Previous resultsshowed that pre-treated mice, but not that treated with high fiber diet (pectin), which presents a potential prebiotic effect, showed a reduction in colonic inflammatory response induced by five dextran sulfate sodium (DSS)-cycles in female BALB/c mice. The first aim of this work was to evaluate the therapeutic use of high fiber diet associated with theprobiotic, Bifidobacterium longum 51A, in the same colitis chronic model described above. Even the high fiber diet, probiotic or association of both therapies were not able to reduce the clinical and histopathological scores of the experimental colitis, a type of IBD model, in animals that received DSS. Showing that, in the experimental design used,the preventive intervention was more efficient rather than therapeutic treatment. Metabolic changes are associated with the inflammatory response and, therefore, another objective of the present study was to study the progression of systemic metabolic alterations, in the adipose tissue and the liver of mice with acute and chronic DSS-inducedcolitis. Female BALB/c mice subjected to experimental acute colitis showed metabolic adaptations such as: a reduction in glycaemia and an increase in total cholesterol and triglycerides concentrations; followed by a reduction in glucose-6-phosphatase and pyruvate kinase expressions in the liver of DSS mice; hepatic fat content reduction and increase in oxidative stress in this organ. Acute colitis induced adipose tissueinflammation associated with reduction in adiponectin and resistin, and increase in leptin concentration. Taken together, these initial adaptations led to glucose intolerance and insulin resistance in chronic colitis, similar to metabolic syndrome, such as: increased glucose, total cholesterol, triglycerides levels, among others. Since leptin levels was altered in the acute and chronic phase of experimental intestinal inflammation and because of its proinflammatory characteristics, another objective of the present study was to evaluate the role of leptin in inflammatory bowel response. Lack of leptin signaling, in db/db mice, induced protection against intestinal inflammation due to reduction in neutrophils and eosinophils cells in the large intestine and, consequently, reduction intissue damage induced by the DSS. These results demonstrate the role of leptin as a contributing factor for the experimental intestinal inflammatory response as well as the clear association between metabolism and inflammatory response. The alteration of itsconcentrations, in both acute and chronic phases of disease, composes a complex scenario of metabolic adaptations/alterations, aforementioned, which could increase the risk of secondary chronic diseases observed in IBD. Key word: colitis, fiber diet, metabolic alteration, liver, adipose tissue, leptin.