INTESTINAL ASSIMILATION OF HYDROPHOBIC MOLECULES

人类注射各种疏水或脂溶性分子。

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.