Characterization Of Hepatic Lipid Metabolism In Apc^Min/+ Mice

In recent years,researchers have found that the incidence and mortality of colorectal cancer?CRC?has gradually increased.It has become one of the malignant tumors that threaten the health of human life.On one hand,the occurrence and development of CRC is closely related to human lifestyle and dietary preferences.On the other hand,it is closely related to the expression and regulation processes of multiple protooncogenes and tumor suppressor genes in the body.The adenomatous polyposis coli?APC?as a tumor suppressor gene,when its function is lost,directly participates in the signaling pathway of Wnt/?-catenin regulating cell adhesion,growth,differentiation,proliferation,and apoptosis,which eventually induces intestinal adenoma hyperplasia.The researchers found that CRC patients showed weakened body weight,reduced food intake,and a marked increase in blood lipid levels.In this study,we used the animal model of familial adenomatous polyposis?FAP?,Apc^Min/+mice,to explore the relationship between liver lipid metabolism and hyperlipidemia.Our study found that:?1?The expression of the lipid synthesis genes?Srebp-1c,Acc1,and Acly?was decreased by qRT-PCR and Western Blot analysis of liver tissue,indicating a decrease in liver lipid de novo lipogenesis?DNL?in WT and Apc^Min/+mice.?2?The gene expression?Cpt1,Cpt2 and Cact?involved in the mitochondrial fatty acid?-oxidation key enzyme in the liver of Apc^Min/+mouse was not different from that in wild-type?WT?mouse.?3?Compared with the 8th,14th and 20th week old Apc^Min/+mice,the ability of Apc^Min/+mice to secrete VLDL-TG gradually decreased with the deterioration of intestinal adenoma in the hepatic triglyceride production test?HTPT?.?4?Down-regulation of GPIHBP1 gene expression is associated with hyperlipidemia in liver of Apc^Min/+mouse.?5?The NF-?B signaling pathway affects the expression level of GPIHBP1 by regulating the transcription factor Oct-1 activity in the HepG2cell line and liver tissues of Apc^Min/+mice.Altogether,our study demonstrated that disordered hepatic lipid metabolism plays an essential role in hypertriglyceridemia.Additionally,the transcription factor Oct-1 influences the GPIHBP1 expression,which is involved in hypertriglyceridemia in Apc^Min/+mice via the NF-?B pathway.This study provides new therapeutic targets and ideas for human clinical treatment of CRC.