Sepsis and Obesity: study of the relationship between obesity and immune regulation in an experimental model of sepsis

Abstract

Obesity and metabolic syndrome are public health problems and influence the outcome of various immune diseases, besides acting as a risk factor for the severity of sepsis. The activation of innate immunity may lead to inflammation of low intensity in obesity by activation of endothelial cells, adipocytes and macrophages and synthesis of TNF-alfa, insulin resistance, and is also linked to diabetes. In addition, there are data that clearly show that obesity may be related to changes in intestinal microbiota and seems to be a risk factor "dose dependent" mortality and morbidity in sepsis. Among the genes associated with obesity, leptin has a central role. Leptin, a 16 Kd protein, is well known for its control functions of appetite and, more recently, their involvement in intestinal inflammation and sepsis. However, little is known about the exact mechanism involved in leptin signaling in cell activation and tissue dysfunction associated with sepsis. But there are indications that high leptin levels are induced by increased production of IL-1 beta and TNF- alfa during sepsis. Thus, the objective of this project is to study the relationship between obesity, leptin and intestinal microbiota in the regulation of immune response in an experimental model of sepsis in obese animals. We aim thus to contribute to understanding the relationship between obesity, gut microbiota and the regulation of immune response during an inflammatory stimulus such as severe sepsis.