INTESTINAL ASSIMILATION OF HYDROPHOBIC MOLECULES

人类会损伤各种各样的疏水或脂溶分子。 虽然这些物质中的许多都是必需的微量营养素或药物，但许多 其他的是有毒的和致癌的。常见的例子包括化石燃料 碳氢化合物、增塑剂、维生素A、D、E和K、许多药物和食物 添加剂，以及许多污染物和生防剂(如： 多氯联苯、杀虫剂和除草剂)。从来没有一个令人满意的 解释这种疏水化学物质(10%的水溶解度 至-8至-10至-14M)可在消化过程中分散，以及 正因为如此，人们通常认为他们的表现很差 全神贯注。我们已经发现，如果疏水的溶质(如 致癌物苯并(A)芘)溶解在饮食中的脂肪液滴中 定量地共分散、共吸收、共运输和共结合 随着脂肪进入细胞内的脂肪小滴在肠细胞。这些 然后对未精炼的脂肪液滴进行酶“加工”， 在进入循环之前被选择性地提纯。这一概念 不分青红皂白地吸收脂肪，然后细胞内处理 为脂质同化提供了一个全新的视角，具有深刻的 对人类健康和疾病的意义；它解释了一个大家庭是如何 具有重要生物学意义的分子可以以高密度进入人体 浓度，它提供了一种机制来解释食物链放大 在外源物质中，它揭示了原本无法溶解的致癌物是如何 高浓度吸收(食用油往往严重 被致癌物质污染和高脂肪饮食与增加 许多人类癌症的发病率)，它揭示了一种简单的方法 疏水药物输送。拟议研究的目的是 确定膳食脂肪的定性和定量承载能力 在脂肪同化过程中的疏水分子，并确定脂肪 可以携带溶质穿过微绒毛膜和细胞质。活体内 示踪和显微镜实验以及体外实验 微绒毛膜囊泡、细胞内脂滴和可溶性 胞浆蛋白将被用来帮助剖析 肠道脂肪同化过程。

Humans injest a wide variety of hydrophobic or fat soluble molecules. While many of these substances are necessary micronutrients or drugs, many others are toxic and carcinogenic. Common examples include fossil fuel hydrocarbons, plasticizers, vitamin A, D, E, and K, many drugs and food additives, and numerous pollutants and biological control agents (e.g. PCBs, pesticides and herbicides). There has never been a satisfactory explanation of how such hydrophobic chemicals (aqueous solubilities of 10 to the -8 to 10 to the -14M) could be dispersed during digestion, and because of this it has generally been assumed that they are poorly absorbed. We have discovered that if a hydrophobic solute (such as the carcinogen benzo(a)pyrene) is dissolved in dietary fat droplets it will be quantitatively codispersed, coabsorbed, cotransported and coincorporated with the lipid into intracellular fat droplets in the enterocyte. These droplets of unrefined fat are then enzymatically "processed" and selectively purified before entering the circulation. The concept of indiscriminate lipid absorption followed by intracellular processing provides a completely new view of lipid assimilation that has profound significance for human health and disease; it explains how a large family of biologically important molecules can enter the body in high concentrations, it offers a mechanism to explain food chain magnification of xenobiotics, it reveals how otherwise insoluble carcinogens can be absorbed in high concentrations (edible oils are often seriously contaminated with carcinogens and high fat diets correlate with increased incidence of many human cancers), and it reveals a simple method of hydrophobic drug delivery. The aim of the proposed research is to determine the qualitative and quantitative carrying capacity of dietary fat for hydrophobic molecules during fat assimilation and to determine how fat can carry solutes through the microvillus membrane and cytosol. In vivo tracer and microscopy experiments and in vitro experiments with isolated microvillus membrane vesicles, intracellular fat droplets, and soluble cytosolic proteins will be conducted to help dissect the steps in the process of intestinal fat assimilation.