Research On The Elements Regulating Angptl3 Expression And The Relationship Between Angptl3 And Metabolic Syndrome

Objective To observe the effects of five elements including glucose, insulin, cholesterol, hexadecylic acid and simvastatin on angiopoientin-like protein 3(ANGPTL3) expression in human liver cells (L02), and glucose on it expression in insulin resistant L02 cells (IR-L02). To investigate the difference of ANGPTL3 serum content between the normal and the patients with hyperglycaemia, patients with high cholesterol, patients with hyperglycaemia and high cholesterol. In order to explore the elements and mechanisms of ANGPTL3 expression regulation, it's function in the development of metabolic syndrome and diabetes mellitus complic hyperlipoproteinemia as well.Methods①L02 cells were incubated separately in mediums containing different concentration of glucose, insulin, cholesterol, hexadecylic acid and simvastatin for 24 hours. Insulin resistant L02 cells, which were induced with high concentration of insulin, were incubated separately in mediums containing different concentration of glucose. The relative level of ANGPTL3 mRNA expression was detected by reverse transcription-polymerase chain reaction (RT-PCR). The relative level of ANGPTL3 protein was measured by western blotting.②The difference of ANGPTL3 serum content was detectived by western blotting between the normal and the patients with hyperglycaemia, patients with high cholesterol, patients with hyperglycaemia and high cholesterol.Results①High level glucose stimulated ANGPTL3 expression both in L02 cells and IR-L02 cells compared with the control group (P<0.01). IR-L02 cells were more sensitive than L02 cells to the same level glucose (P<0.05).Both ANGPTL3 mRNA expression and protein expression increased with the glucose concentration added (P<0.05).②Insulin suppressed ANGPTL3 expression in L02 cells compared with the control group (P<0.01), which relied on the insulin concentration (P<0.05).③Cholesterol and hexadecylic acid increased ANGPTL3 expression in L02 cells compared with the control group (P<0.01).And it depended on the concentration of them (P<0.05).④Simvastatin depressed ANGPTL3 expression in L02 cells compared with the control group (P<0.01), which relied upon its concentration (P<0.05).⑤The ANGPTL3 serum content of the patients with hyperglycaemia, patients with high cholesterol, patients with hyperglycaemia and high cholesterol was higher than it of the normal(P<0.01).Compared with the others, patients with hyperglycaemia and high cholesterol have notable higher ANGPTL3 content in serum(P<0.05). Conclusions①Insulin resistant L02 cells model was established by being induced with high concentration of insulin.②High level glucose can upregulate ANGPTL3 expression. ANGPTL3 may play an important role in diabetes mellitus complic hyperlipoproteinemia. High plasma glucose may be a critical reason for lipid metabolic disturbance in patients with diabetes.③Insulin can downregulate ANGPTL3 expression in liver cells, which depends on its concentration.In addition, insulin may suppress the increase of ANGPTL3 expression induced by high glucose.④High cholesterol and hexadecylic acid may upregulate ANGPTL3 expression in liver cells.⑤Simvastatin may downregulate ANGPTL3 expression in liver cells which relies on its concentration.And it may depress the increase of ANGPTL3 expression induced either by high cholesterol or by high hexadecylic acid.⑥Cholesterol may regulate ANGPTL3 expression as well as glucose, and their upregulating effects may be synergistical in vivo.