Lipid and Apolipoprotein Size Profile Differences Between Low and High Body Mass Index Individuals in Response to Fat Challenge

Clearance of elevated triglycerides (TG) level in response to fat challenge is a clinically significant indicator of CVD risk. HDL can play a key role in facilitating TG metabolism explaining the reverse correlation of HDL levels with CVD risk. In this study 6 individuals, low BMI (21-25) and 3 high BMI (30-49) were challenged with a meal containing ~90 g of total fat. Blood samples were drawn in fasting state before meal and 3 times after meal in 2, 4 and 6 hours. Serum was analyzed by a quantitative, multiplexed analytical workflow which included analysis of whole serum and the separation of lipoproteins by asymmetric flow field-flow fractionation where fractions were collected with 1 nm increments of 7-15 nm (HDL), 20-30 nm (LDL) and >30 nm lipoprotein classes. Dynamic light scattering was used to determine hydrodynamic size in each size fraction. Whole serum and individual fractions were analyzed to determine concentrations of apolipoproteins (apo A-I, A-II, A-IV, B, C-I, C-II, C-III and E), and non-polar lipids (FC, CE and TG), using two parallel liquid chromatography tandem mass spectrometry methods developed in our laboratory. In whole serum, the total TG levels for low and high BMI donors, relative to pre-meal levels (57-137 mg/dL and 111-183 md/dL), peaked at between the 2 and 4 hours post meal (103-214 mg/dL and 210-309 mg/dL). LCAT were lower (20%) and CETP levels were higher (30%), in low vs high BMI groups, but did not show change in repose to the fat challenge. In both low and high BMI groups, the most significant change between pre-meal and post-meal after 2 hours occurred in HDL-ApoC-I, HDL-ApoC-II, and HDL-ApoC-III levels mainly in the HDL size range of 9-12 nm (medium HDL) and at 13-16 nm (large HDL), with concurrent TG increase observed in LDL and remnant fractions (Prob-