Department of Pathology, The University of Texas Medical Branch, Galveston, Texas 77030, USA.
Alcohol Clin Exp Res. 2010 Nov;34(11):1937-47. doi: 10.1111/j.1530-0277.2010.01283.x.
Hepatic steatosis (fatty liver), an early and reversible stage of alcoholic liver disease, is characterized by triglyceride deposition in hepatocytes, which can advance to steatohepatitis, fibrosis, cirrhosis, and ultimately to hepatocellular carcinoma. In the present work, we studied altered plasma and hepatic lipid metabolome (lipidome) to understand the mechanisms and lipid pattern of early-stage alcohol-induced-fatty liver.
Male Fischer 344 rats were fed 5% alcohol in a Lieber-DeCarli diet. Control rats were pair-fed an equivalent amount of maltose-dextrin. After 1 month, animals were killed and plasma collected. Livers were excised for morphological, immunohistochemical, and biochemical studies. The lipids from plasma and livers were extracted with methyl-tert-butyl ether and analyzed by 750/800 MHz proton nuclear magnetic resonance (¹H NMR) and phosphorus (³¹P) NMR spectroscopy on a 600 MHz spectrometer. The NMR data were then subjected to multivariate statistical analysis.
Hematoxylin and Eosin and Oil Red O stained liver sections showed significant fatty infiltration. Immunohistochemical analysis of liver sections from ethanol-fed rats showed no inflammation (absence of CD3 positive cells) or oxidative stress (absence of malondialdehyde reactivity or 4-hydroxynonenal positive staining). Cluster analysis and principal component analysis of ¹H NMR data of lipid extracts of both plasma and livers showed a significant difference in the lipid metabolome of ethanol-fed versus control rats. ³¹P NMR data of liver lipid extracts showed significant changes in phospholipids similar to ¹H NMR data. ¹H NMR data of plasma and liver reflected several changes, while comparison of ¹H NMR and ³¹P NMR data offered a correlation among the phospholipids.
Our results show that alcohol consumption alters metabolism of cholesterol, triglycerides, and phospholipids that could contribute to the development of fatty liver. These studies also indicate that fatty liver precedes oxidative stress and inflammation. The similarities observed in plasma and liver lipid profiles offer a potential methodology for detecting early-stage alcohol-induced fatty liver disease by analyzing the plasma lipid profile.
肝脂肪变性（脂肪肝）是酒精性肝病的早期和可逆阶段，其特征是肝细胞内甘油三酯沉积，可进展为脂肪性肝炎、纤维化、肝硬化，最终发展为肝细胞癌。本研究旨在通过研究改变的血浆和肝脂质代谢组（脂质组）来了解早期酒精诱导性脂肪肝的机制和脂质模式。
雄性 Fischer 344 大鼠以 5%酒精喂养 Lieber-DeCarli 饮食。对照大鼠以等量的麦芽糖糊精喂养。1 个月后，处死动物并收集血浆。切除肝脏进行形态学、免疫组织化学和生化研究。用甲基叔丁基醚提取血浆和肝脏中的脂质，并在 600MHz 谱仪上用 750/800MHz 质子核磁共振（¹H NMR）和磷（³¹P）NMR 光谱分析。然后对 NMR 数据进行多元统计分析。
苏木精和伊红以及油红 O 染色的肝切片显示出明显的脂肪浸润。乙醇喂养大鼠肝组织切片的免疫组织化学分析显示无炎症（无 CD3 阳性细胞）或氧化应激（无丙二醛反应或 4-羟壬烯醛阳性染色）。血浆和肝脏脂质提取物¹H NMR 数据的聚类分析和主成分分析显示，乙醇喂养大鼠与对照组大鼠的脂质代谢组存在显著差异。肝脂质提取物的³¹P NMR 数据显示磷脂的变化与¹H NMR 数据相似。血浆和肝脏的¹H NMR 数据反映了几种变化，而比较¹H NMR 和 ³¹P NMR 数据提供了磷脂之间的相关性。
我们的研究结果表明，饮酒改变了胆固醇、甘油三酯和磷脂的代谢，这可能导致脂肪肝的发生。这些研究还表明，脂肪肝发生在氧化应激和炎症之前。血浆和肝脏脂质谱的相似性为通过分析血浆脂质谱检测早期酒精诱导性脂肪肝提供了一种潜在的方法。
