title: The transport of DDT from chylomicrons to adipocytes does not mimic triacylglycerol transport.
abstract: Despite being banned in the U.S., organochlorine toxins such as DDT are frequently detected in human adipose tissue. The main route of exposure is through the consumption of contaminated foods and subsequent intestinal packaging of DDT into chylomicrons. These chylomicrons, which also contain dietary triacylglycerol (TG), are delivered directly to peripheral tissues without first being metabolized by the liver. The physiological process by which these compounds are delivered from chylomicrons to adipose is not well understood, but is clinically relevant since it bypasses first-pass metabolism. Based on its highly lipophilic nature, it has been assumed that DDT is transferred to peripheral tissues similar to TG; however, this has not been measured. Here, we use the lymph fistula rat to isolate chylomicrons containing both DDT and TG. These chylomicrons are the in vivo DDT delivery vehicle. Using 3T3-L1 adipocytes, we investigated the rate at which DDT transfers from chylomicrons to adipocytes, and mediators of this process. This novel approach closely approximates the in vivo DDT exposure route. We show that: 1) DDT repartitions from chylomicrons to adipocytes, 2) this transport does not require hydrolysis of TG within the chylomicron, and is stimulated by the inhibition of LPL, 3) albumin does not inhibit DDT uptake, 4) DDT dissolved in DMSO does not appropriately mimic in vivo DDT transport; and most importantly, 5) DDT uptake from chylomicrons does not mimic the uptake of TG from the same particles. Understanding these factors is important for designing interventions for human populations exposed to DDT.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH, 45237, USA. alison.kohan@uc.edu
authors.forename: Alison B
authors.initials: AB
authors.lastname: Kohan
authors.forename: Abbey E
authors.initials: AE
authors.lastname: Vandersall
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Jandacek
authors.forename: Patrick
authors.initials: P
authors.lastname: Tso
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D002914:Chylomicrons / Q000378:metabolism*; D003634:DDT / Q000493:pharmacokinetics*; D006868:Hydrolysis; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D002914:Chylomicrons; D014280:Triglycerides; D003634:DDT