A sinalização do Receptor de Toll 4 nos hepatócitos, e não no sistema imune, é a principal via para alterações metabólicas hepáticas durante a Endotoxemia

Abstract

The liver is the main metabolic organ in the body, and hepatocytes – functional units responsible for the hepatic metabolism of carbohydrates, lipids, xenobiotics, etc. – constitute about 80% of the cell population present in this organ. However, the liver also houses a vast population of immune cells that are in constant activity, whose main component is the hepatic resident macrophages: Kupffer cells. Kupffer cells are macrophages present in large numbers in the hepatic sinusoids, where they perform functions such as “filtering” the blood that passes through the liver, which may contain antigens. One of these antigens that may be present is bacterial lipopolysaccharide (LPS), which, when circulating in the sinusoids, can trigger an inflammatory response from TLR4 membrane activation in Kupffer cells. However, another liver cell, not originally considered as an immune cell, can also have TLR4 activated on its membrane in the presence of LPS, thus triggering an immune response: the hepatocytes. Therefore, knowing that there is a presence of a common receptor to the hepatic immune and metabolic compartments, and that these can be activated with consequent generation of an immune response in the organ by both parties, we seek to understand through this project if happens, how it works and what are the metabolic consequences generated by the interaction between these hepatic compartments after an LPS insult.