To investigate how cholesterol induces hepatocytic steatosis, we investigated the effect of cholesterol on hepatic lipogenesis and the assembly and secretion of very-low-density lipoprotein-triglycerides (VLDL-TGs) in goose primary hepatocytes. We found that cholesterol at 20 μg/ml increased the concentrations of extracellular VLDL, intracellular cholesterol, and intracellular TGs, while cholesterol at 30 μg/ml had a reduced effect (p < 0.05). Additionally, cholesterol at 20 μg/ml, but not at 10 or 30 μg/ml, increased the extracellular TG concentration. Cholesterol increased the fatty acid synthase (FAS) enzyme activity in a dose-dependent manner. Incubation with cholesterol increased the mRNA level of genes involved in lipogenesis, including sterol regulatory element-binding proteins (SREBPs), FAS, acetyl-CoA carboxylase-α (ACCα), and liver X receptors. The mRNA level of the acyl-CoA: diacylglycerol acyltransferase 1 (DGAT1) gene changed in response to cholesterol treatment in a dose-dependent manner. Similar to the regulation of extracellular VLDL and intracellular TG accumulation, the mRNA levels of the microsomal triglyceride transfer protein, forkhead box O1, and DGAT2 increased with treatment with 10 or 20 μg/ml of cholesterol, but decreased with treatment with 30 μg/ml of cholesterol (p < 0.05). Cholesterol had no evident effect on the mRNA level of the apolipoprotein B gene. Incubation with cholesterol at 20 and 30 μg/ml increased the nuclear SREBP-1 protein level (p < 0.05) and the binding affinity of the nuclear SREBP-1 to ACCα SRE probes. In conclusion, cholesterol not only activates the transcription of genes involved in fatty acid synthesis and TG accumulation, but also activates the transcription of genes involved in the assembly and secretion of VLDL-TG in goose primary hepatocytes.

In this study, we examined gene expression in order to identify genes that are differentially expressed between the hepatocytes of Sichuan White geese and Landes geese. We hypothesized that such genes may be involved in the different predispositions between these two species to develop hepatic steatosis. RNA was isolated from primary hepatocytes of the two species, and suppression subtractive hybridization was employed to screen for genes that showed differences in mRNA expression. We built and characterized two reciprocal cDNA libraries that were enriched in genes up-regulated in Landes geese or Sichuan White geese. Using dot blot analysis we identified 128 of 600 randomly selected sequences that demonstrated differential expression between the two species. Of these differentially expressed genes, 115 sequences shared high homology with 46 known genes and 13 sequences corresponded to eight novel expressed sequence tags (ESTs). Based on functional clustering, up and down-regulated genes were mostly related to lipid metabolism, nuclear mRNA splicing, enzyme activity and transcription control. The expression of 18 selected clones was further studied by quantitative PCR. The data showed that eight clones similar to the genes ACSL5, CTGF, CIDEA, PPARγ, PCK, GSTS1, RPS4X, and THBS1 had significantly higher expression levels in the hepatocytes of Landes geese. In contrast, seven clones similar to the genes ADH5, YBX1, ASAH1, UCB, AOPVLDL, SCD-1, and ELOVL-6 had significantly higher expression levels in the hepatocytes of Sichuan White geese.

In this study, we investigated the role of liver X receptor (LXR) activation in hepatic assembly and in the secretion of very low density lipoprotein-triglycerides in goose primary hepatocytes. Goose primary hepatocytes were isolated and treated with the LXR agonist T0901317. Total triglyceride accumulation, intracellular and extracellular triglyceride concentrations, extracellular very low density lipoprotein concentration, and gene expression levels of LXRα, microsomal triglyceride transfer protein, acyl coenzyme A:diacylglycerol acyltransferase (DGAT) 1, and DGAT2 were measured in primary hepatocytes. We found a dose-dependent upregulation of total and intracellular TG accumulation when using 0, 0.01, 0.1, 1, and 10 μM T0901317, but the extracellular triglyceride and very low density lipoprotein concentrations were dose dependent only when the T0901317 concentration was below 1 μM; as compared with 1 μM T0901317, 10 μM T0901317 had an inhibiting effect (P < 0.05). The mRNA levels of all the detected genes increased in the presence of T0901317. The change in LXRα and DGAT1 was dose dependent, and the mRNA levels of microsomal triglyceride transfer protein and DGAT2 increased with a T0901317 concentration up to 1 μM, but decreased when treated with 10 μM T0901317 (P < 0.05). In conclusion, the secretion of very low density lipoprotein plays a role in pharmacologically activating the LXR-induced development of hepatocellular steatosis in geese.

Purpose: The purpose of this study was to investigate the relationship between dyslipidemia and lumbar disc herniation (LDH). Methods: A total of 269 patients with LDH and 269 patients with lumbar vertebral fracture (LVF) were enrolled in this study. The total cholesterol level (TC), Low-density lipoprotein-cholesterol level (LDL-C), triglyceride level (TG), High-density lipoprotein-cholesterol level (HDL-C), nonHDL-C, ApoB level, ApoB A1 level and arteriosclerosis index (AI) were measured.The 269 patients with single-level LDH underwent surgery were enrolled as the disc herniation group and 269 patients who underwent surgical treatment for spine fracture(Pfirrmann Grading Systems of Grade I or II) during the same period were enrolled as the control group. The participants in the control group were selected randomly and matched for age (within 5 years) and sex. Results: In this analysis, we found that the level of TC, TG, LDL, nonHDL-C, APOB, and APOA1 in patients with LDH was significantly higher compared with that of the controls. The proportion of high TC, borderline high-total cholesterol, high LDL-C,high TG, borderline high LDL-C, high APO B, high AI and high ApoB/ApoA1 in the LDH group was significantly higher relative to that of the control group. The ratio of TC/HDL-C, TG/HDL-C, LDL-C/HDL-C, nonHDL-C/HDL-C and ApoB/ApoA1 in the LDH group was significantly higher compared with that of the control group. Multivariate logistic regression analysis indicated that the levels of serum LDL-C, TC, TG, nonHDL-C, Apo B and AI were positively associated with the risk of LDH and were independent risk factors predicting LDH development. Conclusion: Overall, this study indicates that TC, TG, LDL-C, nonHDL-C, Apo B, and AI levels in may increase the risk of LDH.Dyslipidemia may be associated with cartilage endplate (CEP) degeneration and hence may be involved in the pathological process of intervertebral disc degeneration (IVDD). Moreover, dyslipidemia may be a useful predictor of IVDD.

The aim of our study was to evaluate the effect of overfeeding on mRNA expression levels of genes involved in lipogenesis, in order to understand the mechanism of hepatic steatosis in the goose. Using Landes geese (Anser anser) and Sichuan White geese (Anser cygnoides) as experimental animals, we quantified the mRNA expression of lipogenic genes, acetyl-CoA carboxylase-α (ACCα) and fatty acid synthase (FAS), and of two transcription factors, sterol regulatory element-binding proteins-1 (SREBP-1) and carbohydrate responsive element-binding protein (ChREBP) by real-time polymerase chain reaction (RT-PCR), and measured the lipid and triglyceride (TG) content in the liver and the plasma level of glucose, insulin and TG. Our results indicated that compared to the control group, the overfeeding induced an increase of the lipid and TG content in the liver and also of the plasma insulin and TG concentration in both breeds. However, the plasma glucose level decreased after overfeeding in the Sichuan White goose, and there was no evident change in the Landes goose. Lastly, the mRNA expression of ACCα, FAS, SREBP-1 and ChREBP in the overfed group was lower than in the control group in both breeds. We concluded that the lipogenesis pathway plays a role in overfeeding-induced hepatic steatosis and that the decreased mRNA level of related genes may be the indicator of hepatic steatosis.