Metabolismo del hierro y de la serotonina en la enfermedad del hígado graso no alcohólico

Identificador:  TDX:3975

Handle: https://hdl.handle.net/20.500.11797/TDX3975

Autors:  Binetti, Jessica Angela

Resum:
This work is based on the study of the metabolism of iron and serotonin (5-HT), potentially involved in the development and progression of non-alcoholic fatty liver disease (NAFLD). NAFLD has become the most common cause of liver disease, along with obesity and the metabolic syndrome. Iron metabolism, through hepcidin (HEPC) and possibly 5-HT seem to intervene in the pathophysiology of NAFLD. The knowledge of these pathways in NAFLD is scarce. In this sense, two studies were conducted in morbidly obese women (MO) with NAFLD. On the one hand, plasma levels of HEPC were analyzed and it was shown that they are associated with obesity but not with the presence of NAFLD or with histological severity. On the other hand, the association between the hepatic expression of HEPC and its regulatory genes involved in iron metabolism and the expression of the main genes of hepatic lipid metabolism was studied, and a clear relationship between them was evidenced, possibly because they share a common pathogenic mechanism. In the second study, plasma levels of 5-HT were analyzed and it was observed that they are decreased in patients with MO on a hypocaloric diet and that 5-HT could have a protective effect on obesity and metabolic syndrome. In addition, the expression of hepatic and jejunal mRNA of serotonin receptors (HTR) was investigated and it was observed that there is a deregulation of hepatic HTR2A and HTR2B in women with MO and NAFLD. No significant differences were found in the jejunal expression levels of HTR3 and HTR4 according to the presence of NAFLD. Although more studies are needed, modulation of iron and 5-HT metabolism could represent future therapeutic targets in obesity and NAFLD.