Thomson A B, Keelan M, Wild G E
Division of Gastroenterology, University of Alberta, Edmonton.
Clin Invest Med. 1996 Oct;19(5):331-45.
The authors review the physiological, cellular and molecular aspects of the patterns, mechanisms and signals of the adaptation of intestinal transport of sugars and lipids, especially in response to manipulations of dietary lipid content. In models of intestinal adaptation, nutrient uptake is enhanced by an up- or down-regulation of the maximal rate of carrier-mediated transport or by alterations in the passive permeability properties (Pd) of the intestinal brush border membrane (BBM). The importance of unstirred water layers has been demonstrated. Alterations in the Pd for lipid uptake are due to changes in the lipid content of the BBM, which in turn are associated with alterations in the activity of lipid-metabolizing enzymes in the enterocyte microsomal membrane (EMM), and, therefore, alterations in the lipid composition of the EMM. Lipid uptake is also mediated by at least two proteins in the BBM, the sodium-hydrogen exchangers and the membrane-fatty-acid-binding protein. Alterations in the maximal transport rate for glucose and fructose transporters are associated with variations in the abundance of their transporters (including sodium-dependent glucose transporter, glucose and fructose transporter and fructose transporter) in the basolateral membrane sodium-potassium adenosine triphosphatase, and in the abundance of the messenger RNA of the transporters. Isocaloric changes in dietary lipids, such as switching from a saturated to a polyunsaturated diet, within the range seen in human consumption, leads to major alterations in passive and active transport processes. In a proposed model, changes in dietary lipids stimulate intracellular second messengers, modifying gene expression of the transporter carriers and of the EMM lipid-metabolizing enzymes. Thus, an understanding of the mechanisms of intestinal adaptation lays the groundwork for future studies of dietary manipulations. It may also lead to dietary interventions to prevent unwanted or to enhance desirable intestinal adaptation, thereby preventing disease.
作者回顾了糖和脂质肠道转运适应性的模式、机制及信号的生理学、细胞和分子方面,特别是对饮食脂质含量变化的反应。在肠道适应性模型中,营养物质的摄取通过载体介导转运的最大速率上调或下调,或通过肠道刷状缘膜(BBM)被动通透性特性(Pd)的改变而增强。已证明了未搅动水层的重要性。脂质摄取Pd的改变是由于BBM脂质含量的变化,这又与肠细胞微粒体膜(EMM)中脂质代谢酶活性的改变相关,因此也与EMM脂质组成的改变相关。脂质摄取还由BBM中的至少两种蛋白质介导,即钠氢交换体和膜脂肪酸结合蛋白。葡萄糖和果糖转运体最大转运速率的改变与它们在基底外侧膜钠钾三磷酸腺苷酶中的转运体丰度变化有关,也与转运体信使核糖核酸的丰度变化有关。在人类饮食摄入范围内,饮食脂质的等热量变化,如从饱和饮食转变为多不饱和饮食,会导致被动和主动转运过程的重大改变。在一个提出的模型中,饮食脂质的变化刺激细胞内第二信使,改变转运体载体和EMM脂质代谢酶的基因表达。因此,了解肠道适应机制为未来饮食干预研究奠定了基础。它还可能导致饮食干预,以预防不良的或增强理想的肠道适应,从而预防疾病。