Research On The Role Of Exenatide In Nonalcoholic Fatty Liver Disease (NAFLD) And The Molecular Mechanism Of It Regulates The Homocysteine (Hcy)

Nonalcoholic fatty liver disease (Nonalcoholic fatty liver diseases, NAFLD) is a disease with lipid metabolism disorder in liver cell, which in turn leads to excessive fatty degeneration and deposition in the liver, but there is no history of heavy drinking, In addition to denaturation liver fat deposits,Its pathological features may be associated with liver cell damage, mixed inflammatory cells infiltration and fibrosis, etc. In recent years, a growing body of research suggests that NAFLD may has a certain relationship with Hyperhomocysteinemia(HHcy). In our previous studies have found that NAFLD often accompanied with a growing level of Homocysteine(Hey), it may be one of the important reasons that late NAFLD leads to atherosclerosis and a variety of cardiovascular diseases.In addition, HHcy probably cause Insulin resistance (IR), in NAFLD,often accompanied by IR. So, the rise of Hey in NAFLD, may be one of the reasons why the disease appeared IR. Therefore, it will improve IR caused by NAFLD by lowering the Hey level in NAFLD. At present, it’s rarely reported on the reduction of Hey and drugs to improve IR in NAFLD,it has a wide attention in recent years by the medical profession on choosing drugs to reduce the Hey understanding the role of molecular mechanisms and treatment of NAFLD and its complications IR, but there is no doenying that we still haven’t found the relevant specific medicine so far, so, it’s a research hot spot to choose effectively drugs to reduce Hey in treatment of NAFLD and its complication in the medical community. The nature of enatide is a analogue of incretin Glucagons-like peptide 1(Glp-1), it is mainly used in diabetes at present, and it can improve IR, the experimental research related with fatty liver is rarely reported at home and abroad, but previous studies have shown that exenatide has a effect on lowering blood sugar and fat, reducing, the deposition of fat in the liver, improving enzymes related with lipid metabolism, alleviate NAFLD and IR.According to the reports and early research foundation, we put forward that exenatide can improve NAFLD and its complications through regulating the expression of Hey metabolic enzymes, reducing the content of Hey in NAFLD. But the specific experimental results remains to be further research. Therefore, this research through the establishment of the NAFLD rats animal models induced by high-fat diet, treated with different concentrations and different action time of exenatide, observing the pathological changes of liver of rats after treatment, detecting the changes of blood lipid, liver function index, glucose, insulin and Hcy, such as detecting the oxidation and anti-oxidation ability in plasma and liver, calculating the insulin resistance index, discussing the mRNA and protein expression changes of the factors related with regulation of Hcy metabolism Methylenetetrahydrofolate reductase(MTHFR) and Methionine synthase(MTR). Research shows that in NAFLD rats model, hepatic steatosis aggravated,blood lipid, blood glucose, insulin increased, liver is damaged, insulin resistance index increased, antioxidant capacity reduced, Hcy concentration increased, is related with the downregulating of MTHFR and MTR participated in the degradation of Hcy,but the MTHFR is mainly factor, After exenatide treatment, the above phenomeno is improved. Therefore, we believe that:1.Establish NAFLD rats model with a high-fat diet, the rats can reach middle or high level of nonalcoholic fatty liver disease model in 12 weeks.2. In NAFLD, abnormality of lipid metabolism can lead to liver steatosis, decrease the liver function, and antioxidant capacity. Steatosis, liver function and antioxidant capacity were improved after exenatide treatment.3. The content of Hcy increased in NAFLD, its mechanism may be mainly associated with MTHFR downgrade. The role of the MTR is not important.4.The Hcy levels is reduced after exenatide treatment, the mechanism is mainly the expression of MTHFR and the content of its cofactors FA increasd 5. It can reduce Hcy levels after exenatide treatment, the mechanism is to upregulate the expression of MTHFR and MTR cause the degradation of Hcy, it may be one of the mechanisms that exenatide alleviate the complication (IR) of NAFLD.