cyclin-d1 and Non-alcoholic-Fatty-Liver-Disease

To investigate the change of plasma nesfatin-1 concentration in a nonalcoholic fatty liver disease rat model induced by high-fat diet, and explore its effect on the dysfunction of glucose and lipid metabolism.. The nonalcoholic fatty liver disease rat model was established through introduction of a high-fat diet, and four weeks later, the intraperitoneal glucose tolerance test was conducted. Serum concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), total cholesterol (TC) triglyceride (TG), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C) were detected using chemiluminescence technique. The plasma levels of nesfatin-1, leptin, and insulin (INS) were measured via enzyme-linked immunosorbent assay (ELISA), the histological changes of the liver was observed via HE staining, and the protein expressions of beta-catenin, p-beta-catenin and cyclin D1 in the liver were detected using western blot and compared with beta-actin.. The bodyweight, liver weight, liver index, and area under the curve of the intraperitoneal glucose tolerance test were all higher in the model rats than those in the controls. Compared with the control, serum concentrations of ALT, TBIL, IBIL, TC and LDL-C in the model rats were all increased. The plasma nesfatin-1 level was increased in model rats while the plasma concentrations of leptin and insulin were decreased, and a negative correlation was found between the plasma concentration of nesfatin-1 and leptin. Inflammation and hepatocyte steatosis were detected in the livers of model rats, and the protein expression of cyclinD1 was upregulated while the phosphorylation of beta-catenin was decreased in the livers of the model rats.. Post-creation of nonalcoholic fatty liver disease rat models through high fat diets, changes were observed in plasma nesfatin-1 concentration, perhaps a vital part of glucose and lipid metabolism dysfunction.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; beta Catenin; Bilirubin; Body Weight; Calcium-Binding Proteins; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cyclin D1; Diet, High-Fat; DNA-Binding Proteins; Enzyme-Linked Immunosorbent Assay; Glucose Tolerance Test; Insulin; Insulin Resistance; Leptin; Lipid Metabolism; Liver; Nerve Tissue Proteins; Non-alcoholic Fatty Liver Disease; Nucleobindins; Rats; Triglycerides

Liver cancer is a major health-care concern and its oncogenic mechanisms are still largely unclear. Persistent hepatocyte cell death is a common feature among various chronic liver diseases, the blocking of which presents as logical treatment. Therefore, we aimed at investigating tumor development in mice with hepatocyte-specific Bid depletion--a BH3-only Bcl-2 family member that amplifies apoptotic death signals. Hepatocyte-specific conditional Bid-knockout mice (Bid(Δhep)) were injected with 25 mg/kg diethylnitrosamine (DEN) at 14 days of age, and liver tumorigenesis was investigated 9 months later. Additionally, different models of acute liver injury were used including: acute high-dose DEN challenge, 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet and carbon tetrachloride (CCL4) injection. Bid(Δhep) mice developed significantly fewer tumors, showed smaller maximal and average tumor size and reduced tumor incidence. In the acute DEN model, 48 h post injection we observed a significant reduction in liver injury in Bid(Δhep) animals, assessed via serum transaminases and liver histopathology. Furthermore, TNF-α, IL-1ß, cJUN and IL-6 mRNA expression was reduced. These findings were accompanied by reduced compensatory hepatocyte proliferation in Bid(Δhep) mice when compared with controls by immunohistochemistry for Ki67 and proliferating cell nuclear antigen 48 h after DEN injection. In the acute CCL4 model, Bid(Δhep) mice displayed reductions in liver injury and inflammation when compared with controls. No differences in liver injury and serum bilirubin levels were detected in Bid(Δhep) and Bid(flo/flo) mice fed with DDC, which induces bile duct injury and a ductular reaction. Our study demonstrates that in DEN-induced hepatocellular carcinoma, the inhibition of hepatocyte death pathways through Bid deletion protects animals from tumorigenesis. These results suggest that reducing hepatocyte cell death, liver inflammation and compensatory proliferation has a stronger beneficial effect than the potential side effect of enhancing tumor cell survival.

Topics: Animals; BH3 Interacting Domain Death Agonist Protein; Carbon Tetrachloride; Cell Proliferation; Cells, Cultured; Chemical and Drug Induced Liver Injury; Cyclin D1; Diethylnitrosamine; Disease Models, Animal; Hepatocytes; Hydrogen Peroxide; Inflammation; Interleukin-6; Liver; Liver Neoplasms; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Non-alcoholic Fatty Liver Disease; Pyridines; Tumor Necrosis Factor-alpha