This article is available online at http://www.jlr.org regulated in a tissue-specifi c manner ( 1, 2 ). As an example, the activity in adipose tissue is relatively low between meals but rises postprandially ( 6 ). This has been suggested to govern when and to what extent lipids are delivered to the adipose tissue for storage ( 1, 2 ). On the other hand, it has been argued that the only role of the enzyme is to release the fatty acids in a form that can be transferred from lipoproteins into cells or onto albumin, and that the amount taken up by individual cells is usually governed by transport processes ( 7 ) and/or the metabolic balance within the cell ( 8 ) rather than by the rate at which the lipase releases fatty acids at endothelial sites adjacent to the cell.The first step in chylomicron catabolism is that the lipoprotein particles bind to the endothelial surface, a process named margination. Goulbourne et al. ( 9 ) have demonstrated that the margination requires LPL bound to GPIHBP1. Defi ciency of GPIHBP1, genetic or in mouse models, leads to equally severe hyperchylomicronemia as defi ciency of LPL itself ( 10 ). In this setting normal amounts of LPL are produced, but do not reach the endothelial surface. Mouse genetic models with altered expression of LPL have been generated. Total LPL defi ciency due to gene knockout leads to lethal hypertriglyceridemia within 18 h of life ( 11 ). By mating heterozygous LPL knockout mice with transgenic mice that express human LPL in either muscle ( 12 ) or heart ( 13 ), mouse lines have been generated that express the enzyme in only a single tissue. Here we have taken advantage of these mouse models to study to what extent the expression of LPL in a tissue governs initial binding and/or deposition of lipids in that tissue . For this we used rat chylomicrons, labeled in vivo with [3 H]-retinol (which is incorporated into retinyl esters and serves as label for the core lipids and for the chylomicron particles) and [ ]retinol (primarily in ester form, providing a tracer for the core lipids) were injected. TG label was cleared more rapidly than core label. There were no differences between the mouse lines in the rate at which core label was cleared. Two minutes after injection, about 5% of the core label, and hence chylomicron particles, were in the heart of WT mice. In mice that expressed LPL only in skeletal muscle, and had much reduced levels of LPL in the heart, binding of chylomicrons was reduced to 1%, whereas in mice that expressed LPL only in the heart, the binding was increased to over 10%. The same patterns of distribution were evident at 20 min when most of the label had been cleared. Thus, the amount of LPL expressed in muscle and heart governed both the binding of chylomicron particles and the assimilation of chylomicron lipids in the tissue.