| [ Summary ] |
The discovery of leptin in 1994 represented a tremendous breakthrough in the field of obesity and the regulation of energy balance. Now, leptin is also known to be a regulatory factor influencing the immune system, insulin secretion, angiogenesis, wound healing and the pathophysiology of liver disease e.g. NASH (non-alcoholic steatohepatitis). NASH seems to develop as a progressive hepatic disease from fatty depositions in the liver. It is believed that this progression involves two steps. The first step is the accumulation of fatty acids, resulting in steatosis associated with insulin resistance strongly related to obesity. The mechanism of this first process involves oxidation of mitochondria' fatty acids, which are blocked by insulin. The second process leads to the occurrence of necrosis, inflammation and fibrosis. This involves oxidative stress by cytochrome P450 2E1 induced with fatty acids. Due to this process, leptin should be added to the list of factors which may play crucial roles in the development of liver fibrosis. Stellate cells may be activated directly or indirectly by leptin with the interaction of Kupffer cells or endothelial cells. Clinical studies have also indicated that hyperleptinemia is a common finding in obese patients and this group of subjects has been shown to have a higher prevalence of fibrosis during chronic HCV infection and have worse prognoses for alcoholic liver disease. |