Organochlorine compounds (OCs) are toxic, carcinogenic, and ubiquitous in the environment. Oral ingestion is the principal route of entry into the human body for many OCs. Because of the lipophilicity of OCs and many of their metabolites, they are preferentially stored in adipose tissue, but are also found in liver, brain, and other organs and tissues. Although oral ingestion is the initial step in the accumulation of OCs in animals and humans, the processes involved in absorption from the intestine and early transport in blood and lymph are not well characterized. We propose studies that will shed light on these important steps in absorption and transport to provide a basic framework that can lead to understanding the ways that nutrients influence the absorption processes.
In Specific Aim 1, we will determine the mode of absorption and association of OCs with carriers in lymph and the portal blood and whether this is affected by the amount and the type of lipid fed. We demonstrated that labeled hexachlorobenzene (HCB) carried in chylomicrons is cleared from the circulation faster than the labeled fatty acid (FA) as part of the triglyceride (TG). To explain this finding, the labeled HCB must not have been dissolved in the TG lipid core of the chylomicron. If it is, then its rate of removal from the circulation should be slower or at best equal to that of the labeled TG. Consequently, in Specific Aim 2, we will determine the mode of delivery of labeled OCs to the tissues (especially the adipose tissue) by proteins, phospholipids, and chylomicrons (CMs). We will also determine the partitioning of HCBs between chylomicrons and any membranes it comes in contact with e.g., red blood cell membrane. Lastly, in Specific Aim 3, we will determine if the relative importance of vehicle (albumin, lipid, or lipoprotein) carrying the labeled OC in blood is altered as a result of weight loss or weight gain (i.e. changes in body fat). The proposed research is important because of the biological and clinical importance of OCs in health and disease and they provide considerable new insights into how OCs are carried and delivered to the various organs in the body.
|Richard, Caroline; Lewis, Erin D; Goruk, Susan et al. (2017) Feeding a Mixture of Choline Forms to Lactating Dams Improves the Development of the Immune System in Sprague-Dawley Rat Offspring. Nutrients 9:|
|Trevaskis, Natalie L; Caliph, Suzanne M; Nguyen, Gary et al. (2013) A mouse model to evaluate the impact of species, sex, and lipid load on lymphatic drug transport. Pharm Res 30:3254-70|
|Kohan, Alison B; Vandersall, Abbey E; Yang, Qing et al. (2013) The transport of DDT from chylomicrons to adipocytes does not mimic triacylglycerol transport. Biochim Biophys Acta 1831:300-5|
|Lu, Wendell J; Yang, Qing; Yang, Li et al. (2012) Chylomicron formation and secretion is required for lipid-stimulated release of incretins GLP-1 and GIP. Lipids 47:571-80|
|Jandacek, R J; Rider, T; Keller, E R et al. (2010) The effect of olestra on the absorption, excretion and storage of 2,2',5,5' tetrachlorobiphenyl; 3,3',4,4' tetrachlorobiphenyl; and perfluorooctanoic acid. Environ Int 36:880-3|
|Jandacek, Ronald J; Rider, Therese; Yang, Qing et al. (2009) Lymphatic and portal vein absorption of organochlorine compounds in rats. Am J Physiol Gastrointest Liver Physiol 296:G226-34|
|Lu, Wendell J; Yang, Qing; Sun, William et al. (2008) Using the lymph fistula rat model to study the potentiation of GIP secretion by the ingestion of fat and glucose. Am J Physiol Gastrointest Liver Physiol 294:G1130-8|
|Lo, Chun-Min; Samuelson, Linda C; Chambers, James Brad et al. (2008) Characterization of mice lacking the gene for cholecystokinin. Am J Physiol Regul Integr Comp Physiol 294:R803-10|
|Lu, Wendell J; Yang, Qing; Sun, William et al. (2007) The regulation of the lymphatic secretion of glucagon-like peptide-1 (GLP-1) by intestinal absorption of fat and carbohydrate. Am J Physiol Gastrointest Liver Physiol 293:G963-71|
|Lo, Chun Min; Zhang, Dian Ming; Pearson, Kevin et al. (2007) Interaction of apolipoprotein AIV with cholecystokinin on the control of food intake. Am J Physiol Regul Integr Comp Physiol 293:R1490-4|