Abstract
The extent to which lipid and apolipoprotein (apo) concentrations in tissue fluids are determined by those in plasma in normal humans is not known, as all studies to date have been performed on small numbers of subjects, often with dyslipidemia or lymphedema. Therefore, we quantified lipids, apolipoproteins, high density lipoprotein (HDL) lipids, and non-HDL lipids in prenodal leg lymph from 37 fasted ambulant healthy men. Lymph contained almost no triglycerides, but had higher concentrations of free glycerol than plasma. Unesterified cholesterol (UC), cholesteryl ester (CE), phosphatidylcholine (PC), and sphingomyelin (SPM) concentrations in whole lymph were not significantly correlated with those in plasma. HDL lipids, but not non-HDL lipids, were directly related to those in plasma. Lymph HDLs were enriched in UC. However, as the HDL cholesterol/non-HDL cholesterol ratio in lymph exceeded that in plasma, whole lymph nevertheless had a lower UC/CE ratio than plasma. Lymph also had a significantly higher SPM/PC ratio. The lymph/plasma (L/P) ratios of apolipoproteins were as follows: A-IV > A-I and A-II > C-III and E > B. Comparison with the L/P ratios of seven nonlipoprotein proteins suggested that apoA-IV was predominantly lipid free. Concentrations of apolipoproteins A-II, A-IV, C-III, and E in lymph, but not of apolipoproteins A-I or B, were positively correlated with those in plasma. The L/P ratios of apolipoproteins B, C-III, and E in two subjects with lipoprotein lipase (LPL) deficiency, and of apolipoproteins A-I and A-IV in a subject with lecithin:cholesterol acyltransferase (LCAT) deficiency, were low relative to those in normal subjects. Thus, the concentrations of lipids, apolipoproteins, and lipoproteins in human tissue fluid are determined only in part by their concentrations in plasma. Other factors, including the actions of LPL and LCAT, are at least as important.
Highlights
The extent to which lipid and apolipoprotein concentrations in tissue fluids are determined by those in plasma in normal humans is not known, as all studies to date have been performed on small numbers of subjects, often with dyslipidemia or lymphedema
Such extravascular events cannot be adequately studied by sampling plasma, as lipoproteins entering blood from tissue fluids are immediately mixed with plasma lipoproteins, and are altered by interactions with them and with several enzymes
This study represents the first attempt to determine the extent to which interindividual differences in the concentrations of the major lipids and apolipoproteins, and those of high density lipoprotein (HDL) and non-HDL lipids, in peripheral tissue fluid are determined by their concentrations in plasma in normal humans
Summary
The extent to which lipid and apolipoprotein (apo) concentrations in tissue fluids are determined by those in plasma in normal humans is not known, as all studies to date have been performed on small numbers of subjects, often with dyslipidemia or lymphedema. The difficulties of sampling tissue fluid under physiologic conditions and in sufficient quantities for studies of Abbreviations: apo, apolipoprotein; CE, cholesteryl ester; HDL, high density lipoprotein; LCAT, lecithin:cholesterol acyltransferase; LDL, low density lipoprotein; LPL, lipoprotein lipase; L/P ratio, lymph/plasma ratio; PC, phosphatidylcholine; PL, phospholipid; SPM, sphingomyelin; TC, total cholesterol; TG, triglyceride; TGRL, triglyceride-rich lipoprotein; UC, unesterified cholesterol. This collection procedure has major problems: a high failure rate (typically 50%), low flow rates (usually 50–100 L/h), a short cannulation life (typically 1 –3 h) and the need to preinject a dye subcutaneously to visualize the vessel Because of these difficulties, most studies of human lymph lipoproteins have involved small numbers of subjects (usually 4–6), often with lipid disorders, or have been limited to patients with lymphedema. We describe the technique, and report our initial findings
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