| As you know, liver is the most important organ in our bodies for energy and metabolism, so it is for fat. Nowadays, for the reason of meal, hepatic steatosis has been the second in lists of liver disease, seriously, more and more youngers are prone to get it.There are two kinds of liver steatosis, including alcoholic fatty liver disease (AFLD) and nonalcoholic fatty liver disease (NAFLD). Because NAFLD is not easy to detect in the early stage, so it becomes the focus in current studies. Chronic high fat (HF) diet plays an important role in NAFLD, and liver is the most important organ for lipid metabolism, so it is certainly meaning to study how HF influence the liver in the process of NAFLD, and what is the most important site to regulate in curing the disease.ApoE is the apolipoprotein for chylomicra (CM), very low density lipoprotein (VLDL) and high density lipoprotein (HDL), by recognizing the receptor on the surface of cell, it can bring lipoprotein into cells, in order to oxidize, transform into lipid, or store. Low density lipoprotein receptor (LDLR) is the main receptor of low density lipoprotein. ApoE/LDLR double deficient (AL-/-) mice are not able to transfer lipoproteins into liver or cells, so it's easier to get hypertriglyceride and hypercholesteremia. Current studies related to NAFLD mostly focused on obesity and insulin resistance, there were less studies about the effect of HF diet, especially for AL-/- mice.In this experiment, AL-/- mice were divided into 2 groups. One group was fed with HF diet and the other with CHOW for 6, 10 18 and 34 weeks. Semi-RT-PCR assay was used to detect the most key regulators and proteins in the fatty acid oxidation. Combining with the pathomorphological characteristics of liver, and the lipid concentrations in plasma and liver, we studied the effects of HF diet on the development of NAFLD.The results showed us that compared with mice fed with CHOW, the expression of 1iver fatty acid binding protein (L-FABP) in the group of HF diet elevated at ages of 6, 10 and 18W, especially for 18W there was a significant difference (P<0.05). And peroxisome proliferators-activated receptor-γcoactivator (PGC-1α) also significantly raised in 6 and 34W (P<0.05), at the age of 10W, it was slightly higher than CHOW diet, but lower in 18W, neither were significantly different.Peroxisome proliferator-activated receptorα(PPARα) is the key regulator of fatty acid oxidation, in this study the expression of PPARαdescended in HF group, but there was no significant difference between the two groups.Carnitine palmitoyl transferase I (CPT I), cytochrome oxidase (COX I), uncoupling protein (UCP2) all play important roles in the process of fatty acidβ-oxidation in mitochondria. The results showed us that the expressions of those genes were all up-regulated in livers of HF mice at mRNA level. But only at the age of 18W, there was a significantly difference for COX I (P<0.05).25~50% fatty acid are metabolized in peroxisome, in order to study the oxidation of fatty acid in peroxisome, we detected the expression of acyl-CoA oxidase (ACOX1), which is the key enzyme inβ-oxidation of peroxisome, it raised up in the group of HF diet, but there was no significant difference.Endoplasmic reticulum is the place of fatty acidω-oxidation, the family of cytochrome P450 including CYP2E1 and CYP4A10 are both genes regulated by PPARα. In the results, expressions of CYP2E1 and CYP4A10 descended in the group of HF diet. At ages of 10 and 34W, there were significant difference between the two groups for CYP2E1 (P<0.05).Acetyl-CoA carboxylase (ACC1) is the most important enzyme in synthesis of fatty acid in liver, the results showed that the mRNA of ACC1 at ages of 6 and 10W significantly elevated in HF group than CHOW group (P<0.05). And it cut down to be lower than CHOW diet significantly at ages of 18W (P<0.05) and 34 W (P<0.01).Serum TC, LDL-C and HDL-C of different ages were significantly different in two groups (P<0.01), the level of TG was higher in group of HF diet significantly at ages of 6 and 10W (P<0.05), and it was greatly significant in 18 and 34W (P<0.01).The analysis of liver extraction showed us that the concentration of free fatty acid (FFA) was higher greatly in group of HF diet at ages of 6 and 10W (P<0.01), and it was lower at ages of 18 and 34W for mice fed with HF diet. The concentration of total lipid in livers of the mice was measured, the data told us it was significantly higher in mice of HF diet (P<0.05). The content of TG in liver was significantly higher in HF diet at the age of 6W (P<0.05). After that, the level of TG was degraded to be lower than that of CHOW diet at ages of 10, 18 and 34W significantly (P<0.05).
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