Comparison of the effect of post-heparin and pre-heparin lipoprotein lipase and hepatic triglyceride lipase on remnant lipoprotein metabolism
Introduction
Remnant lipoprotein (RLP) metabolism is known to be regulated by lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) [1], [2], [3]. LPL plays a central role in triglyceride-rich lipoproteins (TRLs) metabolism by catalyzing the hydrolysis of triglycerides (TG) in chylomicrons (CMs) and very low-density lipoprotein (VLDL) particles and is a useful biomarker in diagnosing Type I hyperlipidemia [4] and also prediction of cardiovascular diseases [5]. HTGL has been recognized to play a role in catalyzing the hydrolysis of the smaller remnants into LDL [6]. We previously reported that postprandial RLPs in a 4 h period after a fat load are significantly larger in particle size compared to the fasting state, with a TG increase in RLPs [7]. The interaction of those lipase activities with the associated lipoproteins and RLP particle size in the fasting and postprandial plasma was the focus of this investigation.
The accumulation of RLPs of large particle size after an oral fat load is mainly due to the delayed metabolism of VLDL by LPL [7], [8]. LPL and HTGL activities and concentrations, both with and without a heparin injection, were pursued in order to elucidate the plasma TRL metabolism, especially in terms of the effect on the RLP particle size, estimated by RLP-TG/RLP-C ratio compared with HPLC assay by Okazaki et al. [9]. If there is a close similarity between the RLP particle size in pre- and post-heparin plasma, it may be possible to eliminate the heparin injection that is commonly used to measure LPL and HTGL activities and concentrations for clinical diagnostic purposes. Non-heparinized plasma (pre-heparin plasma) is known to contain a considerably large amount of LPL, but the activity of TG hydrolysis is very low or non-detectable. Watson et al. [10] tried to measure this low level of LPL activity by increasing the serum volume and prolonging the incubation time, but they still did not find a meaningful association between the pre-heparin LPL activity and the lipoprotein concentrations, suggesting that the plasma LPL concentration does not reflect a significant role in lipid metabolism, at least via its lipolytic activity.
However, recent studies have revealed that catalytically inactive LPL in pre-heparin plasma can act as a ligand for lipoprotein receptors and glucosaminoglycans in the liver [11], [12], [13], [14], [15]. Thus, catalytically inactive LPL might participate in lipoprotein metabolism via its ligand function rather than its lipolytic function. Because it is catalytically inactive, the measurement of pre-heparin LPL concentration has not received much attention as a diagnostic marker in clinical laboratories, despite the extensive studies reported by Shirai and et al. [16], [17], [18], [19], [20], [21], [22], [23] and others [24], [25].
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Study subjects
The study in relatively healthy young volunteers (some cases were overweight or obese) in a male (n = 36) and female (n = 40) population (Caucasian 45, Asian 10, Hispanic 9, African American 7, others 5) with a median age of 24 and BMI of 24 at the University of California, Davis (Table 1). Inclusion criteria included age from 18 to 40 y and BMI of 18–35 kg/m2 with a self-report of stable body weight during the prior 6 months. Exclusion criteria included evidence of diabetes, renal disease, or hepatic
Post-heparin plasma lipids, lipoproteins, LPL and HTGL activity and concentration analyses in the fasting and postprandial states.
Table 1 indicates the demographic data on 76 volunteers recruited at UC Davis, CA. Table 2 indicates that the mean total cholesterol (TC), LDL-C and HDL-C levels were within a normal range in the fasting and postprandial plasma. TG, RLP-C, and RLP-TG were significantly elevated in the postprandial plasma, but TC, LDL-C, HDL-C and sdLDL-C did not change. RLP-TG/RLP-C ratio in the postprandial plasma increased 2.6 fold compared to the fasting plasma both in pre-heparin and post-heparin plasma.
Discussion
We reported previously that postprandial RLPs increased significantly after food intake and exhibited a 4.4 fold increase of RLP-TG/RLP-C ratio in a 4 h period after fat intake reflecting the RLP particle size, along with a specific increase in RLP-TG, which is mainly composed of VLDL remnants [7], [8]. The VLDL remnants, which were not fully metabolized by lipases and remained in the plasma after food intake, have significantly large TG-rich particles. To the best of our knowledge, this is the
Acknowledgments
Authors greatly thank Dr. John Brunzell, the University of Washington, Seattle, WA for his valuable discussions and comments.
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