Young S G, Cham C M, Pitas R E, Burri B J, Connolly A, Flynn L, Pappu A S, Wong J S, Hamilton R L, Farese R V
Gladstone Institute of Cardiovascular Disease, San Francisco, California 94141-9100, USA.
J Clin Invest. 1995 Dec;96(6):2932-46. doi: 10.1172/JCI118365.
The formation of chylomicrons by the intestine is important for the absorption of dietary fats and fat-soluble vitamins (e.g., retinol, alpha-tocopherol). Apo B plays an essential structural role in the formation of chylomicrons in the intestine as well as the VLDL in the liver. We have developed genetically modified mice that express apo B in the liver but not in the intestine. By electron microscopy, the enterocytes of these mice lacked nascent chylomicrons in the endoplasmic reticulum and Golgi apparatus. Because these mice could not form chylomicrons, the intestinal villus enterocytes were massively engorged with fat, which was contained in cytosolic lipid droplets. These mice absorbed D-xylose normally, but there was virtually no absorption of retinol palmitate or cholesterol. The levels of alpha-tocopherol in the plasma were extremely low. Of note, the absence of chylomicron synthesis in the intestine did not appear to have a significant effect on the plasma levels of the apo B-containing lipoproteins produced by the liver. The mice lacking intestinal apo B expression represent the first genetic model of defective absorption of fats and fat-soluble vitamins and provide a useful animal model for studying nutrition and lipoprotein metabolism.
肠道乳糜微粒的形成对于膳食脂肪和脂溶性维生素（如视黄醇、α-生育酚）的吸收至关重要。载脂蛋白B在肠道乳糜微粒以及肝脏极低密度脂蛋白的形成中起着至关重要的结构作用。我们培育出了在肝脏而非肠道中表达载脂蛋白B的转基因小鼠。通过电子显微镜观察，这些小鼠的肠上皮细胞在内质网和高尔基体中缺乏新生的乳糜微粒。由于这些小鼠无法形成乳糜微粒，肠绒毛上皮细胞大量充满了脂肪，这些脂肪包含在胞质脂滴中。这些小鼠能正常吸收D-木糖，但几乎不吸收视黄醇棕榈酸酯或胆固醇。血浆中α-生育酚的水平极低。值得注意的是，肠道中乳糜微粒合成的缺失似乎对肝脏产生的含载脂蛋白B的脂蛋白的血浆水平没有显著影响。缺乏肠道载脂蛋白B表达的小鼠代表了脂肪和脂溶性维生素吸收缺陷的首个遗传模型，并为研究营养和脂蛋白代谢提供了一个有用的动物模型。
