Liver is the place where cholesterol is synthesized, transported, secreted, and transformed, thus liver takes an irreplaceable role in cholesterol homeostasis. Hepatic cholesterol metabolism differs between breeds, yet the molecular mechanism is unclear. In this study Large White (LW) and Erhualian (EHL) piglets (at birth and 25-day-old) were used, 6 each time point per breed. Erhualian piglets had significantly lower body and liver weight compared with Large White at birth and weaning, but the liver/ body weight ratio was higher at weaning, associated with increased serum and liver cholesterol and triglyceride content. The mRNA expression of Cholesterol-7alpha-hydroxylase (CYP7a1) and Recombinant Acetyl Coenzyme Acetyltransferase 2 (ACAT2) were down-regulated in Erhualian piglets at birth, while hepatic Sterol-regulatory element binding protein 2 (SREBP2) mRNA expression was up-regulated in Erhualian piglets at weaning, as well as SREBP2 protein content, compared with Large White piglets. At birth, the depressed CYP7a1 transcription in Erhualian piglets was associated with decreased Histone H3 (H3) and increased Histone H3 lysine 27 trimethylation (H3K27me3). While the results revealed significant promoter hypermethylation of 3-Hydroxy-3-methylglutaryl-CoA reductase (HMGCR) promoter in Erhualian piglets at weaning, together with increased Histone H3 lysine 9 monomethylation (H3K9me1) and Histone H3 lysine 4 trimethylation (H3K4me3). These results suggest that epigenetic modification may be an important mechanism in hepatic cholesterol metabolism among different species, which is vital for maintaining cholesterol homeostasis and decreasing risk of cardiovascular disease.

中文翻译：

---

关键酶CYP7a1和HMGCR的表观遗传调控影响不同仔猪肝脏胆固醇的代谢。

肝脏是胆固醇合成，运输，分泌和转化的地方，因此肝脏在胆固醇稳态中起着不可替代的作用。不同品种的肝胆固醇代谢不同，但分子机制尚不清楚。在这项研究中，使用了大白（LW）和二化lian（EHL）仔猪（出生时和25日龄），每个品种每个时间点6只。与出生时和断奶时的大白猪相比，二化lian仔猪的体重和肝重明显降低，但断奶时肝/体重比更高，这与血清，肝胆固醇和甘油三酯含量增加有关。出生仔猪中胆固醇-7α-羟化酶（CYP7a1）和重组乙酰辅酶乙酰基转移酶2（ACAT2）的mRNA表达下调，与大白猪相比，二化hua仔猪断奶时肝甾醇调节元件结合蛋白2（SREBP2）mRNA表达上调，SREBP2蛋白含量也升高。在出生时，二化lian仔猪的CYP7a1转录降低与组蛋白H3（H3）降低和组蛋白H3赖氨酸27三甲基化（H3K27me3）升高有关。虽然结果显示二化仔猪断奶时3-Hydroxy-3-methylglutaryl-CoA还原酶（HMGCR）启动子有明显的启动子超甲基化，同时组蛋白H3赖氨酸9单甲基化（H3K9me1）和组蛋白H3赖氨酸4三甲基化（H3K4me3）也增加。这些结果表明表观遗传修饰可能是不同物种之间肝脏胆固醇代谢的重要机制，